烧烤肉制品中杂环胺形成规律研究

详细信息    本馆镜像全文|  推荐本文 |  |   获取CNKI官网全文

英文题名：Studies on the Formation Discipline of Heterocyclic Aromatic Amines in Fried Meat 作者：廖国周 论文级别：博士 学科专业名称：食品科学 中文关键词：杂环胺 ; 传统肉制品 ; 前体物 ; 动力学 ; 天然抗氧化剂 ; 抑制 ; 固相萃取 ; 高效液相色谱 英文关键词：Heterocyclic aromatic amines ; Traditional meat products ; Precursor ; Kinetic modeling ; Natural extracts ; Inhibition ; Solid-phase extraction ; HPLC 学位年度：2008 导师：周光宏 学科代码：083201 学位授予单位：南京农业大学 论文提交日期：2008-04-01

摘要

饮食是诱发癌症的一个重要因素,而杂环胺是肉品在高温加工过程中通过美拉德反应与自由基机制而形成的一类致癌致突变化合物。杂环的形成受物理与化学因素的影响,如加工温度与时间,加工方式与设备,以及前体物等。目前肉品加工过程形成的杂环胺已引起研究者的广泛关注,并对杂环胺的各个方面展开研究,如在不同食品中的形成与出现,暴露的水平,生物利用效率,生物转移和致癌性,从而确定其对人类癌症形成的影响。然而中国传统肉制品的加工方法与国外的有较大差异,且国内尚未见相关的研究报道,因此本研究旨在探讨传统烧烤肉制品中杂环胺的形成量与形成机制,并进一步探讨天然抗氧化剂对烧烤肉制品中杂环胺形成的影响。具体研究内容和结果如下:
     1.传统肉制品中杂环胺检测方法的研究
     选取烤鸭、烤羊肉、烧鸡、卤牛肉和肉松5种传统肉制品为对象分析其杂环胺含量,样品净化前处理通过串联Extrelut-PRS-C_(18)柱进行固相萃取,经TSK-gelODS-80TM柱分离并以配备二极管阵列和荧光检测器的HPLC对杂环胺进行测定。结果表明,建立的方法中15种杂环胺的线性范围为0.01 ng·μL~(-1)-1.0 ng·μL~(-1),检测限为0.02 ng·μL~(-1)-0.3 ng·μL~(-1),回收率为61%-94%,相对标准偏差为2.4%-8.0%,该方法达到定量分析的要求。在传统肉制品中检测出6种杂环胺,且不同的肉制品中杂环胺的种类与含量不一致。9H-吡啶并[3,4-6]吲哚(Norharman)与1-甲基-9H-吡啶并[3,4-b]吲哚(Harman)均存在于所有肉制品中,含量分别为42.75 ng·g~(-1)和33.9 ng·g~(-1)。3-氨基-1-甲基-5H-吡啶并[4,3-b]吲哚(Trp-P-2)只存在于烤鸭与烤羊肉中,2-氨基-1-甲基-6-苯基-咪唑并[4,5-b]吡啶(PhIP)在烤鸭、烤羊肉和肉松中检出,而2-氨基-9H-吡啶并[2,3-b]吲哚(AaC)、2-氨基-3-甲基-9H-吡啶并[2,3-b]吲哚(MeAaC)只存在于肉松中,其含量均小于2 ng·g～(-1)。
     2.加工方式对鸭肉中杂环胺形成的影响
     将鸭肉分别进行蒸煮、微波、炭烤、烘烤、油炸与煎烤加工处理,加工鸭肉中的杂环胺分析前处理通过串联Extrelut-PRS-C_(18)柱进行固相萃取,经TSK-gel ODS-80TM柱分离并以配备二极管阵列和荧光检测器的HPLC对杂环胺进行测定。结果表明,加工鸭肉的烹调损失及杂环胺的含量与种类随着加工温度的升高与时间的延长而增加。煎烤鸭肉中形成的杂环胺种类与含量最大,其次为炭烤、油炸、烘烤、微波与蒸煮鸭肉。9H-吡啶并[3,4-b]吲哚(Norharman)与1-甲基-9H-吡啶并[3,4-b]吲哚(Harman)存在于所有加工鸭肉中,其含量在0.1 ng·g~(-1)-33 ng·g~(-1)之间。2-氨基-1-甲基-6-苯基-咪唑并[4,5-b]吡啶(PhIP)在煎烤与炭烤鸭肉中形成较多,含量在0.9 ng·g~(-1)-17.8 ng·g~(-1)之间。2-氨基-3甲基咪唑并[4,5-f]喹啉(IQ)只在煎烤与炭烤鸭肉中检出,含量在0.39 ng·g~(-1)-4.19 ng·g~(-1)之间。2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)在炭烤、烘烤、油炸与煎烤鸭肉中检出,含量高达4.49 ng·g~(-1),其他杂环胺含量均小于10 ng·g~(-1)。加工鸭肉色泽随着加工温度升高而增加,但与杂环胺的形成量不存在相关性。
     3.原料肉中前体物含量对杂环胺形成的影响
     将牛、猪、羊、鸡、鸭和鹅肉分别在200℃下煎烤10 min,分析其原料肉中前体物的含量与加工肉制品中杂环胺的形成量,以探讨不同动物原料肉中杂环胺的形成量及原料肉中前体物的含量对杂环胺形成的影响。结果表明,6种原料肉中前体物含量差异较大,肌酸与葡萄糖的摩尔浓度比在0.89-9.84之间。加工肉制品中共检测出10种杂环胺,其中9H-吡啶并[3,4-b]吲哚(Norharman)与1-甲基-9H-吡啶并[3,4-b]吲哚(Harman)在加工肉品中含量最高,分别在10.90 ng·g~(-1)-24.16 ng·g~(-1)与4.64 ng·g~(-1)-14.04 ng·g~(-1)之间。而2-氨基-3,8-二甲基咪唑并[4,5-f]喹喔啉(MeIQx)在牛肉中形成量较高,达3.55 ng·g~(-1),2-氨基-1-甲基-6-苯基-咪唑并[4,5-b]吡啶(PhIP)在禽肉中易于产生,其中鸡肉中含量最高,达15.26 ng·g~(-1)。PhIP与肌酸和葡萄糖的摩尔浓度比存在相关性(P<0.05),随着葡萄糖浓度的增高,PhIP的形成量减少。
     4.模型体系中杂环胺形成的动力学研究
     以羊肉模型体系为对象对杂环胺形成的动力学进行研究,探讨加热温度、时间及前体物对杂环胺形成的影响。羊肉分别在四个不同温度(160、180、200、220℃)下加热四个时间段(5、10、15、20 min),肉样中形成的杂环胺采用固相萃取并以配合二极管阵列和荧光检测器的HPLC进行分析。结果表明,羊肉中共检出IQ、MeIQx、4,8-DiMeIQx、PhIP、Norharman、Harman、Trp-P-2、Trp-P-1、AaC与MeAaC 10种杂环胺。随着加热温度与时间的增加,杂环胺的形成量增加,220℃下加热20 min,IQ、MeIQx、4,8-DiMeIQx、PhIP、Norharman、Harman、Trp-P-2、Trp-P-1、AaC与MeAaC的形成量分别为4.51 ng·g~(-1)、10.99 ng·g~(-1)、5.75 ng·g~(-1)、7.44 ng·g~(-1)、25.71 ng·g~(-1)、22.04 ng·g~(-1)、2.17 ng·g~(-1)、1.80 ng·g~(-1)、6.55 ng·g~(-1)、6.32 ng·g~(-1)。杂环胺前体物葡萄糖与肌酸的含量随着杂环胺形成量的增加而减少,呈负相关;而肌酸酐则相反,呈正相关。杂环胺形成的机制遵循一种反应物浓度过量的双分子反应机制,为准一级反应。
     5.天然抗氧化剂对烤羊肉中杂环胺形成的影响
     将0.05%VE,0.1%与0.5%葡萄籽提取物,0.1%与0.5槲皮素添加于羊肉表面,分别在200℃下煎烤10 min,利用固相萃取-配备二极管阵列检测器的HPLC分析烤羊肉中15种杂环胺的形成量,以探讨天然提取物对烤羊肉中杂环胺的形成量的影响。结果表明,烤羊肉中共检测出10种杂环胺,其中极性杂环胺4种,非极性杂环胺6种,总量达51.68 ng·g~(-1)。在极性杂环胺中PhIP的形成量较高,达10.50 ng·g~(-1);非极性杂环胺中Norharman与Harman形成量较高,分别达19.66 ng·g~(-1)与12.23 ng·g~(-1)。烤羊肉中添加天然抗氧化剂只对极性杂环胺有抑制作用。其中添加0.05%VE、0.1%槲皮素与0.5%槲皮素对杂环胺抑制作用不明显,添加0.5%葡萄籽提取物可以显著抑制IQ,MeIQx,4,8-DiMeIQx与PhIP 4种极性杂环胺的生成(p<0.05),其生成量分别减少36.65%,67.73%,35.63%与30.00%。天然抗氧化剂对烤羊肉中非极性杂环胺的抑制作用不明显。
Diet is an important factor in the global variation of human cancer. Heterocyclic aromatic amines (HAAs) are mutagenic/carcinogenic compounds formed at low levels via the Maillard reaction and a free radical mechanism during cooking of animal tissue at high temperature. The formation and yield of HAAs are dependent on physical parameters, such as cooking temperature and time, cooking technique and equipment, heat and mass transport, and on chemical parameters, especially the precursors to HAAs. To date, researchers all over the world are busy studying various aspects of HAAs such as their formation, occurrence in different food products, bioavailability, bio-transformation, carcinogenicity, levels of exposure to consumers, in efforts to determine their significance in human cancer development. However, the processing methods and conditions of Chinese traditional food is different from Western, and to date little is known about HAAs content in the traditional meat products of China. The objectives of the present study were to investigate the formation of HAAs in Chinese traditional food, and to evaluate their inhibition through the addition of natural antioxidants to meat before cooking. The contents and results are as follows.
     1. Detection of heterocyclic aromatic amines in traditional meat products by HPLC
     HAAs content was investigated in five traditional meat products (including roasted duck, charbroiled mutton, dried pork floss, marinated beef, roasted chicken). The clean-up procedure included tandem solid-phase extraction (SPE) using Extreltut-type columns filled with diatomaceous earth, propylsulphonic acid and chemically bounded phase-C_(18). Separation was achieved using TSK-gel ODS-80TM column and identification and quantitative analysis of HAAs fraction was carried out using a HPLC system with DAD and FLD. Results showed that the linear ranges were 0.01 ng·μL~(-1)-1.0 ng·μL~(-1) and the limit of detection were0.02 ng·μL~(-1)-0.3 ng·μL~(-1) for 15 HAAs. Recoveries were 61%-94%, the relative standard deviation were 2.4%-8.0%. Six HAAs were detected in the traditional meat products, the various and content of HAAs differentiated among the meat products. 9H-pyrido[4,3-b]indole (Norharman) and 1-methyl-9H-pyrido[4,3-b]indole (Harman) were detected in all of the meat products, and the content of it were up to 42.75 ng·g~(-1), 33.9 ng·g~(-1) respectively. 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) was only detected in roasted duck and charbroiled mutton. 2-amino-1-methyl-6-phenylimidazo [4,5-f]pyridine (PhIP) was detected in roasted duck, charbroiled mutton and dried pork floss. However, 2-amino-9H-pyrido[2,3-b]indole (AaC) and 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAaC) were only detected in dried pork floss. The content of it were less 2 ng·g~(-1).
     2. Formation of heterocyclic aromatic amines during processing of duck meat
     The effects of various processing methods, boiling, microwave cooking, charcoalgrilling, roasting, deep-frying and pan frying on the formation of heterocyclic aromatic amines (HAAs) in duck breast were studied. Results showed that both the varieties and contents of HAAs and the cooking loss of duck breast increasing along with increasing cooking temperature and time. Pan frying of duck breasts contained the highest amount of total HAAs, followed by charcoal grilling, deep-frying, roasting, microwave cooking and boiling. 9H-pyrido[4,3-b]indole (Norharman) and 1-methyl-9H-pyrido[4,3-b]indole (Harman) were detected in all of the cooked duck meat, and the content of it were from 0.1 ng·g~(-1) up to 33 ng·g~(-1). 2-amino-1-methyl-6-phenylirnidazo[4,5-f]pyridine (PhIP) was formed easily in cooked duck meat by pan frying and charcoal grilling, the content of it was from 0.9 ng·g~(-1) up to 17.8 ng·g~(-1). 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) was identified in duck meat by charcoal grilling and pan frying, the content of it was from 0.39 ng·g~(-1) up to 4.19 ng·g~(-1). 2-amino-3, 8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) was detected in amounts below 4.49 ng·g~(-1) in duck meat by charcoal grilling, roasting, deep-frying and pan frying. The other HAAs were detected in amounts below 10 ng·g~(-1). Colour development increases with cooking temperature, but no correlation with HAAs content was observed.
     3. Effect of precursor composition in raw meat on the formation on heterocyclic aromatic amines in pan fried meats
     The meat pieces of following animals species, beef, pork, mutton, chicken, duck and goose were pan fried at 200℃for 10 min to study the occurrence of HAAs in fried meat of various animal species and the effect of precursor composition in raw meat on the formation of HAAs in pan fried meat. The composition of precursor (free amino acids, creatine and glucose) was examined in raw meat and the HAAs were detected in pan fried meat by HPLC with DAD and FLD detection. Results showed that great differences were found between the precursor content, both between the animal species and within any species. The molar ratio of total creatine/glucose was from 0.89 up to 9.84. Ten HAAs were detected in pan fried meat. 9H-pyrido[4,3-b]indole(Norharman) and 1-methyl-9H-pyrido [4,3-b]indole (Harman) were detected at high levels in cooked meat, the concentrations of the two compounds ranged from 10.90 ng·g~(-1) up to 24.16 ng·g~(-1) and from 4.64 ng·g~(-1) to 14.04 ng·g~(-1) respectively. 2-amino-3, 8-dimethyl-imidazo[4,5-f]quinoxaline(MeIQx) was detected in amounts up to 3.55 ng·g~(-1) in beef. 2-amino-1-methyl-6-phenylimidazo-[4, 5-f]pyridine (PhIP) was formed easily in poultry, the content of PhIP in chicken was up to 15.26 ng·g~(-1). A significant linear correlation only existed between PhIP and the molar ratio of total creatine/glucose(P<0.05), the increased glucose contents reduced the concentrations of PhIP.
     4. Kinetics of heterocyclic aromatic amines formation in meat model system
     Mutton was used as a model system to examine the kinetics of the formation ofherterocyclic aromatic amines and elucidate the effects of time, temperature, and precursors on the formation of HAAs in cooked ground mutton. Freshly ground mutton was heated at four different temperatures (160, 180, 200, 220℃) for four different time intervals (5, 10, 15, 20 min). HAAs were extracted and purified using solid-phase extraction and quantified using reverse-phase HPLC equipped with DAD and scanning fluorescence detectors. The results showed that 10 HAAs (IQ, MeIQx, 4, 8-DiMeIQx, PhIP, Norharman, Harman, Trp-P-2, Trp-P-1, AaC and MeAaC) were identified. The formation of HAAs increased with increasing time and temperature. The highest amount of HAAs formation of 4.51 ng·g~(-1), 10.99 ng·g~(-1), 5.75 ng·g~(-1), 7.44 ng·g~(-1), 25.71 ng·g~(-1), 22.04 ng·g~(-1), 2.17 ng·g~(-1)、1.80 ng·g~(-1), 6.55 ng·g~(-1)、6.32 ng·g~(-1), respectively were found after heating for 20 min at 220℃. Glucose and creatine decreased with increasing time and temperature, while creatinine increased with increasing time and temperature. The formation of HAAs and the degradation of precursors were inversely correlated. The formation of HAAs followed a bimolecular mechanism with one reactant concentration in large excess.
     5. Inhibition effect of natural extract on the formation of heterocyclic aromatic amines in cooked mutton
     The effects of vitamin E, grape seed extract and quercetin on HAAs formation in fried ground mutton patties were studied. Antioxidants were added directly to the surface of the patties before frying. Patties were fried at 200℃for 10 min. HAAs were isolated by solid phase extraction and quantitated by HPLC with DAD and FLD detection. Results showed that 10 HAAs were detected in fried ground mutton patties, the total amount of HAAs was up to 51.68 ng·g~(-1). 9H-pyrido[4,3-b]indole (Norharman), 1-methyl-9H-pyrido [4,3-b]indole (Harman) and 2-amino-1-methyl-6- phenylimidazo-[4,5-f]pyridine (PhIP) were detected at high levels in fried ground mutton patties, the concentrations of the two compounds were 19.66 ng·g~(-1),12.23 ng·g~(-1) and 10.50 ng·g~(-1) respectively. Compared to the control, the HAAs were not significantly decreased by 0.05% vitamin E, 0.1% quercetin and 0.5% quercetin, but it showed the decreased trend. IQ was effectively decreased by 0.5% grape seed extract in the treatment compared to the control. IQ concentrations in cooed patties were reduced by 10.32%. Grape seed extract at 0.5% levels significantly reduced the formation of IQ, MeIQx, 4,8-DiMeIQx and PhIP by 36.65%, 67.73%, 35.63%and 30.00% respectively (p<0.05). Antioxidants were not effectively inhibited the formation of apolar HAAs in cooked mutton.

引文

[1] Ferguson L R. Natural and human-made mutagens and carcinogens in the human diet[J]. Toxicology, 2002,181:79-82
    [2] Widmark E M P. Presence of cancer-producing substances in roasted food[J]. Nature, 1939, 143: 984
    [3] Sugimura T, Nagao M, Kawachi T, et al. Mutagens carcinogens in food, with special reference to highly mutagenic pyrolytic products in broiled foods[M]. In Origins of Human Cancer, ed. Hiatt H H, Watson J D, Winsten J A. Cold Spring Harbour Laboratory, New York, 1977,1561-1577
    [4] Commoner B, Vithayathil A J, Dolara P, et al. Formation of mutagens in beef and beef extract during cooking[J]. Science, 1978,201: 913-916
    [5] Felton J S, Knize M G. Heterocyclic aminemutagens/carcinogens in foods[M]. In Handbook of Experimental Pharmacology, ed. Copper C S, Graver P L. Springer-Ver lag, Berlin, 1990,471-502
    [6] Sugimura T, Wakabayashi K, Nagao M. et al. A new class of carcinogens: heterocyclic amines in cooked food. In Food, Nutrition and ChemicalToxicity[M]. eds. Parke D V, Ioannides C, Walker R. Smith-Gordon and Nishimura Ltd, 1993,259-276
    [7] Wakabayashi K, Nagao M, Esumi H, et al. Food-derived mutagens and carcinogens[J].Cancer Research (Suppl.), 1992, 52:2092s-2098s
    [8] Adamson R H, Thorgeirsson U P, Snyderwine E G, et al. Carcinogenicity of 2-amino-3-methylimidazo[4,5-f]-quinoline in nonhuman primates: induction of tumors in three macaques[J]. Japanese Journal of Cancer Research, 1990, 81:10-14
    [9] Adamson R H, Takayama S, Sugimura T, et al. Induction of hepatocellular carcinoma in nonhuman primates by the food mutagen 2-amino-3-methylimidazo-[4, 5-f]quinoline[J]. Environmental Health Perspectives, 1994,102:190-193
    [10] Ohgaki H, Takayama S, Sugimura T. Carcinogenicities of heterocyclic amines in cooked food[J]. Mutation Research, 1991,259: 399-410
    [11] Yoshimi N, Sugie S, Iwata H, et al. Species and sex differences in genotoxicity of heterocyclic amine pyrolysis and cooking products in hepatocyte primary culture/DNA repair test using rat, mouse and hamster hepatocytes[J]. Environmental and Molecular Mutagenesis, 1988,12: 53-64
    [12] 吴永宁，现代食品安全科学[M]，北京：化学工业出版社．2003：261-270
    [13] Ames B N, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with Salmonella/mammalian-microsomal mutagenicity test[J]. Mutation Research, 1975, 31: 347-364
    [14] Nakayasu M, Nakasato F, Sakamoto H, et al. Mutagenic activity of heterocyclic amines in Chinese hamster lung cells with diphtheria toxin resistance as a marker[J]. Mutation Research, 1998,118:91-102
    [15] Thompson L H, Carrano A V, Salazar E, et al. Comparative genotoxic effects of the cooked food related mutagens Trp-P-2 and IQ in bacteria and cultured mammalian cells[J]. Mutation Research, 1983,117:243-257
    [16] Mnuro I C, Kennepohl E, Erickson R E, et al. Safety assessment of ingested heterocyclic amines: initial report[J]. Regulatory Toxicology and Pharmacology, 1993,17: S1-S109
    [17] Lynch A M, Knize M G, Boobis A R, et al. Interindividual variability in systemic exposure in humans to 2-amino-3,8-dimethylimidazo(45-f)quinoxaline and 2-amino-1-methyl-6-phenyl-imidazo(4,5-b)pyridine, carcinogens present in cooked beef[J]. Cancer Research, 1992, 52:6216-6223
    [18] Thompson L H, Tucker J D, Steward S A, et al. Genotoxicity of compounds from cooked beef in repair-deficient CHO cells versus Salmonella mutagenicity[J]. Mutagenesis, 1987,2:483-487
    [19] Okamoto T, Shudo K, Hashimoto Y, et al. Identification of a reactive metabolite of the mutagen, 2-amino-3-methylimidazo[4,5-f]quinoline[J]. Chem. Pharm. Bull. 1981,29: 590-593
    [20] Patterson A M, Chipman J K. Activation of 2-amino-3-methylimidazo-[4,5-f]quinoline in rat and human hepatocyte/Salmonella mutagenicity assays: the contribution of hepatic conjugation[J].Mutagenesis, 1987,2: 137-140
    [21] Turteltaub K W, Knize M G, Buonarati M H, et al. Metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine by liver microsomes and isolated rabbit cytochrome P450 isozymes[J]. Carcinogenesis, 1990, 6:941-946
    [22] Aoyama T, Gelboin H, Gonzalez, F. Mutagenic activation of 2-amino-3-methyl-imidazo[4,5-f] quinoline by complementary DNA-expressed human liver P450[J]. Cancer Research, 1990, 50:2060-2063
    [23] Turesky R J, Lang N P, Butler M A, et al. Metabolic activation of carcinogenic heterocyclic amines by human liver and colon[J]. Carcinogenesis, 1991,12: 1839-1845
    [24] Sinha R, Rothman N, Brown E D, et al. Pan-fried meat containing high levels of heterocyclic aromatic amines but low levels of polycyclic aromatic hydrocarbons induces cytochrome P4501A2 activity in humans[J]. Cancer Research, 1994, 54: 6154-6159
    [25] Ohgaki H, Kusama K, Matsukura N, et al. Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo [4,5-f|quinoline from broiled sardine, cooked beef and beef extract[J]. Carcinogenesis, 1984, 5: 921-924
    [26] Kato T, Ohgaki H, Hasegaawa H, et al. Carcinogenicity in rats of a mutagenic compound, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline[J]. Carcinogenesis, 1988, 9:71-73
    [27] Ito N, Hasegawa R, Sano M, et al. A new colon and mammary carcinogen in cooked food, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine(PhIP)[J]. Carcinogenesis, 1991, 12:1503-1506
    [28] Schiffman M H, Felton J S. Re: fried foods and the risk of colon cancer[J]. American Journal of Epidemiology, 1990,131:376-378
    [29] IARC. Some Naturally Occurring Substances: Food Items and Constituents, Heterocyclic Aromatic Amines and Mycotoxins// IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. No. 56. [R]. International Agency for Research on Cancer, Lyon, 1993
    [30] Felton J S, Malfatti M A, Knize M G, et al. Health risks of heterocyclic amines[J]. Mutation Research, 1997, 376: 37-41
    [31] Layton D W, Bogen K T, Knize M G, et al. Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research[J]. Carcinogenesis, 1995,16: 39-52
    [32] Felton J S, Knize M G, Roper M,et al. Chemical analysis, prevention and low-level dosimetry of heterocyclic amines from cooked food[J]. Cancer Research. 1992, 52(Suppl.): 2103s-2107s
    [33] Deitz A C, Zheng W, Leff M, et al. N-Acetyltranseferase-2 genetic polymorphism, well-done meat intake, and breast cancer risk among postmenopausal women[J]. Carcinogenesis, 2000, 9:905-910
    [34] Marchand I L, Hankin J H, Wilkens L R, et al. Combined effects of well-done red meat, smoking and rapid N-Acetylrransferase 2 and CYP1A2 phenotypes in increasing colorectal cancer risk[J]. Carcinogenesis, 2001,10: 1259-1266
    [35] Felton J S, Knize M G, Wood C, et al. Isolation and characterization of new mutagens from fried ground beef[J]. Carcinogenesis, 1984, 5: 95-102
    [36] Galceran M T, Moyano E, Puignou L, et al. Determination of heterocyclic amines by pneumatically assisted electropray liquid chromatography-mass spectrometry[J]. Journal of Chromarography A, 1996,730: 185-194
    [37] Tikkanen L M, Latva-Kala K J, Heinio R L. Effect of commercial marinades on the mutagenic activity, sensory quality and amount of heterocyclic amines in chicken grilled under different conditions[J]. Food and Chemical Toxicology, 1996, 34: 725-7301
    [38] Turesky R J, Bur H, Huynh-Ba T, Aeschvacher H J, et al. Analysis of mutagenic amines in cooked beef products by high-performance liquid chromatography in combination with mass spectrometry[J]. Food and Chemical Toxicology, 1988, 26: 501-509
    [39] Hayatsu H, Arimotao S, Wakabayashi K. Methods for separation and detection of heterocyclic amine[M]. In Mutagens in Food and Detection and Prevention. Eds, Hayatsu H. CRC Press, Boca Raton, FL, 1983,101-112
    [40] Gross G A. Simple methods for quantifying mutagenic heterocyclic aromatic amines in food products[J]. Carcinogenesis. 1990,11:1597-1603
    [41] Manabe S, Suzuki H, Wada O. and Keki A. Detection of the carcinogen, 2-amino-1- methyl -6-phenylimidazo[4,5-b]pyridine (PhIP), in beer and wine[J]. Carcinogenesis, 1993b, 14: 889-901
    [42] Takahashi M, Waskbayashi K, Nagao M, et al. Quantification of 2-amino-3-methylimidazo [4,5-f]quinoline(IQ) and 2-amino-3-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in beef extracts by liquid chromatography with electrochemical detection(LCEC) [J].Carcimogenesis, 1985, 6:1195-1199
    [43] Gross G A, Griiter A. Quantification of mutagenic/careinogenic heterocyclic aromatic amines in food products[J]. Journal of Chromatography, 1992, 592:271-278
    [44] Gross G A, Turesky R. J, Fay L B, et al. Heterocyclic aromatic amine formation in grilled bacon, beef and fish and in grill scrapings[J]. Carcinogenesis, 1993,14: 2313-2318
    [45] Knize M G, Dolbeare F A, Carroll K L, et al. Effect of cooking time and temperature on the heterocyclic amine content of fried beef patties[J]. Food and Chemical Toxicology, 1994a, 32:595-603
    [46] Skog K, Steineck G, Augustsson K, et al. Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues[J]. Carcinogenesis, 1995, 16:861-867
    [47] Skog K, Augustsson K, Steineck G, et al. Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues[J]. Food and Chemical Toxicology, 1997, 35: 555-565
    [48] (?)vervik E, Kleman M, Berg I, et al. Influence of creatine, amino acids and water on the formation of the mutagenic heterocyclic amines found in cooked meat[J]. Carcinogenesis, 1989, 10: 2293-2301
    [49] Knize M G, Hopmans E, Happe J A. The identification of a new heterocyclic amine mutagen from a heated mixture of creatine, glutamic acid and glucose[J]. Mutation Research, 1991, 260: 313-319
    [50] Kataoka H. Methods for the determination of mutagenic heterocyclic amines and their application in environmental analysis[J]. Journal of Chromarography A, 1997, 774: 121-142
    [51] Pais P, Knize M G. Chromatographic and related techniques for the determination of aromatic heterocyclic amines in foods[J]. Journal of Chromarography B., 2000,747:139-169
    [52] Toms-Barbern F A, Gil M I, Cremin P, et al. HPLC-DAD-ESIMS analysis of phenolic compounds in neetarines, peaches and plums[J]. Journal of Agricultural and Food Chemistry, 2001, 49: 4748-4760
    [53] Kataoka H, Nishioka S, Kobayashi M, et al. Analysis of mutagenic heterocyclic amines in cooked food samples by gas chromatography with nitrogen-phosphorus detector[J]. Bull. Envirin, Contam. Tocicol, 2002,69: 682-689
    [54] Pais P, Moyano F, Puignou L, et al. Liquid chromatography atmospheric-pressure chemical ionization mass spectrometry as a routine method for the analysis of mutagenic heterocyclic amines in beef extract[J]. Journal of Chromarography, 1997, 778: 207-218
    [55] Kataoka H, Pawliszyn J. Development of in-tube solid-phase micro-extraction/liquid chromatography / electrospray ionization mass spectrometry for the analysis of mutagenic heterocyclic amines[J]. Chromatographia, 1999, 50: 532-538
    [56] Barcelo-Barrachina E, Moyano E, Galceran M T. Determination of heterocyclic amines by liquid chromatography-quadrupole time-of-flight mass spectrometry[J]. Journal of Chromatography A,2004,1054: 409-418
    [57] Vanderlaan M, Bruce E, Watkins M H , et al. Monoclonal antibodies for the immunoassay of mutagenic compounds produced by cooking beef[J]. Carcinogenesis, 1988,9:153-160
    [58] Vanderlaan M, Bruce E, Watkins M H , et al. Monoclonal antibodies to 2-amino-1-methyl-6- phenylimidazo[4,5-b] pyridine (PhIP) and their use in the analysis of well-done fried beef[J]. Carcinogenesis, 1989,10:2215-2221
    [59] Van Dyck M M C, Rollmann B, De Meester C. Quantitative estimation of heterocyclic aromatic amines by ion-exchange chromatography and electrochemical detection[J]. Journal of Chromatography A, 1995,697: 377-382
    [60] Stavric B, Lau B P Y, Manila T I, et al. Mutagenic heterocyclic aromatic amines (HAAs) in processed food flavour samples[J]. Food and Chemical Toxicology, 1997a, 35: 185-197
    [61] Skog K I, Johansson M A E, J(?)gerstad M I. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake[J]. Food and Chemical Toxicology, 1998, 36: 879-896
    [62] Richling E, Decker C, Haring D, et al. Analysis of heterocyclic aromatic amines in wine by high performance liquid chromatography electrospray tandem mass spectrometry[J]. Journal of Chromatography A, 1997,791:71-77
    [63] Kasai H, Yamaizmi Z, Wakabaysahi K, et al. Structure and chemical synthesis of MeIQ, a potent mutagen isolated from broiled fish[J]. Chem. Letter, 1980, 11: 1391-1394
    [64] Barnes W S, Maher J C, Weisburger J H. High-pressure liquid chromatographic method for the analysis of 2-amino-3-methylimidazo[4,5-f]quinoline, a mutagen formed during the cooking of food[J]. Journal of Agricultural and Food Chemistry, 1983,31: 883-886
    [65] Sugimura T, Sato S, Wakabayashi K. Mutagens/carcinogens in pyrolysates of amino acids and proteins in cooked foods: heterocyclic aromatic amines[M]. In Chemical Induction of Cancer, Structural Basis and Biological Mechanism. Eds. Woo Y T, Lai D Y, Arcos J C, et al. Academic Press, New York, 1988,681-710
    [66] Johansson M, Jagerstad M. Occurrence of mutagenic/carcinogenic heterocyclic amines in meat and fish products, including pan residues, prepared under domestic conditions[J]. Carcinogenesis, 1994,15:1511-1518
    [67] Yamaizumi Z, Kasai H, Nishimura, S, et al. Stable isotope dilution quantification of mutagens in cooked foods by combined liquid chromatography-thermospray mass spectrometry[J]. Mutation Research, 1986,173: 1-7
    [68] Zhang X M, Wakabayashi K, Liu Z C. Mutagenic and carcinogenic heterocyclic amines in Chinese cooked foods[J]. Mutation Research, 1988,201:181-188
    [69] Vahl M, Gry J, Nielsen P A. Mutagens in fried pork and the influence of frying temperature (Abstract) [J]. Mutation Research, 1988,203:239
    [70] Negishi C, Wakabayashi K, Tsuda M, et al. Formation of 2-amino-3, 7, 8-trimethylhnidazo [4,5-f]quinoxaline, a new mutagen, by heating mixture of creatinine, glucose and glycine[J]. Mutation Research, 1984,140: 55-59
    [71] Grivas S, Nyhammar T, Olsson K, et al. Formation of a new mutagenic DiMeIQx compound in a model system by heating creatinine, alanine and fructose[J]. Mutation Research, 1985, 151:177-183
    [72] Murray S, Lynch A M, Knize M G, et al. Quantification of the carcinogens 2-amino-3,8- dimethyl-and 2-amino-3,4,8-trimethylimidazo[4,5-f|quinoxaline and 2-amino-1-methyl-6-phenylimi-dazo [4,5-b] pyridine in food using a combined assay based on gas chromatography-negative ion mass spectrometry [J]. Journal of Chromatography, 1993,616:211-219
    [73] Murkovic M, Friedrich M, Pfannhauser W. Heterocyclic aromatic amines in fried poultry meat[J]. Zeitschrift fur Lebensmittel-Untersuchung und Forschung A, 1997, 205: 347-350
    [74] Sinha R, Rothman N, Brown E D, et al. High concentrations of the carcinogen 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking[J]. Cancer Research, 1995,55:4516-4519
    [75] Knize M G, Salmon C P, Hopmans E C, et al. Analysis of foods for heterocyclic aromatic amine carcinogens by solid-phase extraction and high performance liquid chromatography[J]. Journal of Chromatography A, 1997a, 763: 179-185
    [76] Thiebaud H P, Knize M G, Kuzmicky P A, et al. Airborne mutagens produced by frying beef, pork and soy-based food[J]. Food and Chemical Toxicology, 1995,33: 821-828
    [77] Lee H, Tsai S J. Detection of IQ-type mutagens in canned roasted eel[J]. Food and Chemical Toxicology, 1991, 29: 517-522
    [78] Skog K, J(?)gerstad M. Effects of monosaccharides and disaccharides on the formation of food mutagens in model systems[J]. Mutation Research, 1990,230:263-272
    [79] Johansson M, Jagerstad M. Influence of oxidized deep-frying fat and iron on the formation of mutagens in a model system[J]. Food and Chemical Toxicology, 1993, 31:971-979
    [80] Felton J S, Knize M G, Shen N, et al Identification of the mutagens in cooked beef[J]. Experimental Health Perspectives, 1986, 67:17-24
    [81] Felton J S, Fultz E, Dolbeare F A, et al. Reduction of heterocyclic aromatic amine mutagens/carcinogens in fried patties by microwave pretreatment[J]. Food and Chemical Toxicology, 1994, 30: 897-903
    [82] Thiebaud H P, Knize M G Kuzmicky P A, et al. Mutagenicity and chemical analysis of fumes from cooking meat[J]. Journal of Agricultural and Food Chemistry, 1994,42:1502-1510
    [83] Skog K, Jagerstad M. Effects of glucose on the formation of PhJP in a model system[J]. Carcinogenesis, 1991,12:2297-2230
    [84] Manabe S, Tohyama K, Wada K. Detection of a carcinogen, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine(PhIP), in cigarette smoke condensate[J]. Carcinogenesis, 1991,12:1945-1947
    [85] Skog K, Knize M G, Jagerstad M, et al. Formation of new heterocyclic amine mutagens by heating creatinine, alanine, threonine, and glucose[J]. Mutation Research, 1992b, 268:191-197
    [86] Gry J, Vahl M, Nielsen P A. Mutagens in fried meat publ[M]. national food administration, Copenhagen, Denmark, 1986, 139
    [87] Knize M G, Roper M, Shen N H, et al. Proposed structure for an amino dimethyli- midazofur-opyridine mutagen in cooked meats[J]. Carcinogenesis, 1990,11: 2259-2262
    [88] Kurosaka R, Wakabayashi K, Ushiyama H, et al. Detection of 2-amino-1-methyl-6-(4-hydroxyphenyl)-imidazo[4,5-b]pyridine in broiled beef[J]. Japanese Journal of Cancer Research, 1992, 83: 919-922
    [89] Reistad R, Rossland O J, Latva-Kala K J, et al. Heterocyclic aromatic amines in human urine following a fried meat meal[J]. Food and Chemical Toxicology, 1997, 35: 945-955
    [90] Wakabayashi K, Kim I-S, Kurosaka R, et al. Identification of new mutagenic heterocyclic amines[M]. In Heterocyclic Amines in Cooked Foods: Possible Human Carcinogens, ed. Adamson R H, J(?)gustavsson N, Ito M, et al. Princeton Scientific Publishing Co, Princeton, NJ. 1995, 197-206
    [91] Chen B H, Meng C N. Formation of heterocyclic amines in a model system during heating[J]. Journal of food protection, 1999, 62: 1445-1450
    [92] Abdulkarim B G, Smith J S. Heterocyclic amines in fresh and processed meat products[J]. Journal of Agricultural and Food Chemistry, 1998,46:4680-4687
    [93] Lansen J, Dragsted L, Frandsen H, et al. Carcinogenicity of mutagen from cooked meats. In Mutagen and Carcinogens in the Diet[M]. Eds. Pariza M W, Aeschbacher J, Felton J S, et al. Wiley-Liss, New York, NY, 1990, 89-108
    [94] J(?)gerstad M, Laser Reutersward A, óste R, et al. Creatinine and Maillard reaction products as precursors of mutagenic compounds formed in fried beef[M]. In The Maillard Reaction in Foods and Nutrition, ed. G Waller and M. Feather, Washington, DC, 1983a, 507-519
    [95] J(?)gerstad M, Laser Reutersward A, Olsson R., et al. Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds: effects of various amino acids[J]. Food Chemistry, 1983b, 12: 239-244
    [96] J(?)gerstad M, Olsson K, Grivas S, et al. Formation of 2-amino-3,8-dimethylimi-dazo[4,5-f| quinoxaline in a model system by heating creatinine, glycine and glucose[J]. Mutation Research, 1984,126:239-244
    [97] Negishi C, Wakabayashi K, Yamaizumi J, et al. Identification of 4, 8-DiMeIQx, a new mutagen [J]. Mutation Research, 1985,147: 267-268(abstract)
    [98] Nyhammar T. Studies on the Maillard reaction and its role in the formation of food mutagens[D]. PhD thesis. 1986, Swedish University of Agricultural Sciences, Sweden.
    [99] Jones R C, Weisburger J H. Inhibition of aminoimidazoquinoxaline-type and aminoimidazol-4-one-type mutagen formation in liquid reflux models by L-tryptophan and other selected indoles[J]. Japanese Journal of Cancer Research, 1988a, 79: 222-230
    [100] Pearson A M, Chen C, Gray J I, et al. Mechanism(s) involved in meat mutagen formation and inhibition[J]. Free Radicals in Biology and Medicine, 1992b, 13:161-167
    [101] Mili(?) B L, Djilas S M, Canadanovi(?)-Brunet J M. Synthesis of some heterocyclic aminoimidazoazarenes[J]. Food Chemistry, 1993, 46: 273-276
    [102] Lee H, Lin M Y, Lin S T. Characterization of the mutagen 2-amino- 3-methylimidazo- [4,5-f] quinoline prepared from a 2-methylpyridine/creatinine/ acetylformaldehyde model system[J]. Mutagenesis, 1994a, 9: 157-162
    [103] Arvidsson P, van Boekel M A J S, Skog K, et al. Kinetics of formation of polar heterocyclic amines in a meat model system[J]. Journal of Food Science, 1997,62: 911-916
    [104] Yaylayan V, Jocelyn ParéJ R R. Laing P.et al (Eds.) The Maillard Reaction in Food Processing, Human Nutrition and Physiology[M], Birkh(?)user, Basel, 1990,115
    [105] Wakabayashi K, Totsuka Y, Fukutome K, et al. Human exposure to mutagenic/ carcinogenic heterocyclic amines and comutagenic β-carbolines[J]. Mutation Research, 1997,376:253-259
    [106] Shioya M, Wakabayashi K, Sato S, et al. Formation of a mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in cooked beef, by heating a mixture containing creatinine, phenylalanine and glucose[J]. Mutation Research, 1987,191:133-138
    [107] Felton J S, Knize M G. Mutagen formation in muscle meats and model heating systems[M]. In Mutagens in Food: Detection and Prevention, ed. Hayatsu H. CRC Press, Boca Raton, FL, 1991, 57-66
    [108] Manabe S, Kurihara N, Wada O, et al. Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating[J]. Carcinogenesis, 1992,13: 827-830
    [109] Z(?)chling Siegfried, Michael Murkovic. Formation of the heterocyclic aromatic amine PhIP: identification of precursors and intermediates[J]. Food Chemistry, 2002, 79:125-134
    [110] Murkovic M, Weber H J, Geiszler S, et al. Formation of the food associated carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in model systems[J]. Food Chemistry, 1999,65: 233-237
    [111] Becher G, Knize M G, Felton J S. Identification and synthesis of new mutagens from afried Norwegian product[J]. Vàr Fòda (Suppl. 2), 1989,42: 85-90
    [112] Becher G, Knize M G, Nes I F, et al. Isolation and identification of mutagens from a fried Norwegian meat product[J]. Carcinogenesis, 1988, 9: 247-253
    [113] Skog K, Knize M G, Felton J S, et al. Formation of new heterocyclic amines mutagens by heating creatinine, alanine, threonine and glucose[J]. Mutation Research, 1992a, 268:191-197
    [114] Kim I S, Wakabayashi K, Kurosaka R, et al. Isolation and identification of a new mutagen, 2-amino-4-hydroxy-methyl-3,8-dimethylimidazo[4,5-f]quinoxaline (4-CH_2OH-8-MeIQx), from beef extract[J]. Carcinogenesis, 1994, 15:21-26
    [115] Nukaya H, Koyota S, Jinno F, et al. Structrural determination of a new mutagenic heterocyclic amine, 2-ammo-1,7,9-trimethylimidazo[4,5-g]quinoxaline(7,9-DiMeIgQx), present in beef extract. Carcinogenesis, 1994,15:1151-1154
    [116] Knize M G, Cunningham P L, Avila J R, et al. Formation of mutagenic activity from amino acids heated at cooking temperatures[J]. Food and Chemical Toxicology, 1994c, 32: 55-60
    [117] Knize M G, Cunningham P L, Grin E A, et al. Characterization of mutagenic activity in cooked grain food products[J]. Food and Chemical Toxicology, 1994b, 32:15-21
    [118] Johansson M A E, Knize M G, J(?)gerstad M, et al. Characterization of mutagenic activity in instant hot beverage powders[J]. Environmental and Molecular Mutagenesis, 1995b, 25, 154-161
    [119] Johansson M A E, Fay L B, Gross G A, et al. Influence of amino acids on the formation of mutagenic/carcinogenic heterocyclic amines in a model system[J]. Carcinogenesis, 1995a, 16:2553-2560
    [120] Wu X, Skog K, J(?)gerstad M. Trigonelline, a naturally occurring constituent of green coffee behind the mutagenic activity of roasted coffee [J]. Mutation Research, 1997, 391:171-177
    [121] Jackson L S, Hargraves W A. Effects of time and temperature on the formation of MeIQx and DiMeIQx in a model system containing threonine, glucose and creatine[J]. Journal of Agricultural and Food Chemistry, 1995,43:1678-1684
    [122] de Meester C, Galceran M T, Rabache M. Chemical analysis of heterocyclic amines (HAAs) in heated processed food: Second intercomparison on the quantitative determination of HAAs in a commercial sample of beef extract[J]. European Commison BCR information, Chemical analysis, 1997, report EUR 17652 EN
    [123] Skog K, Jagerstad M. Incorporation of carbon atoms from glucose into the food mutagens MelQx and 4,8-DiMeIQx using ~(14)C-labelled glucose in a model system[J]. Carcinogenesis,1993,14:2027-2031
    [124] Lee H, Lin M Y, Chan S C. Formation and identification of carcinogenic heterocyclic aromatic amines in boiled pork juice[J]. Mutation Research, 1994b, 308: 77-88
    [125] Koehler P E, Mason M E, Newell J A. Formation of pyrazine compounds in sugar-amino acid model systems[J]. Journal of Agricultural and Food Chemistry, 1969,17: 393-396
    [126] Yoshida D, Matsumoto T, Yoshimura R, et al. Mutagenicity of amino- a-carbolines in pyrolysis products of soybean globulin[J]. Biochem. Biophys. Res. Commun., 1978, 83: 915-920
    [127] Sugimura T. Mutagens, carcinogens, and tumor promoters in our daily food[J]. Cancer, 1982, 49:1970-1984
    [128] Grivas S, Nyhammar T, Olsson K, Jagerstad M. Formation of a new mutagenic DiMeIQx compound in a model system by heating creatinine, alanine and fructose[J]. Mutation Research,1985,151:177-183
    [129] Grivas S, Nyhammar T, Olsson K, et al. Isolation and identification of the food mutagens IQ and MelQx from a heated model system of creatinine, glycine and fructose[J]. Food Chemistry,1986,20:127-136
    [130] Arvidsson P, van Boekel M A J S, Skog K, et al. Formation of heterocyclic amines in a meat juice model system[J]. Journal of food science, 1999,64(2): 216-221
    [131] Borgen E, Solyakov A, Skog K. Effects of precursor composition and water on the formation of heterocyclic amines in meat model systems[J]. Food Chemistry, 2001,74: 11-19
    [132] Cammerer B, Kroh L W. Investigation of contributor of radicals to the mechanism of the early stage of the Maillard reaction[J]. Food Chemistry, 1996,57:217-221
    [133] Roberts R T, Lloyd R V. Free radical formation from secondary amines in the Maillard reaction[J].Journal of Agricultural and Food Chemistry, 1997,45: 2413-2418
    [134] Johansson M, Jagerstad M. Influence of pro-and antioxidants on the formation of mutagenic/ carcinogenic heterocyclic amines in a model system[J]. Food Chemistry, 1996, 56: 69-75
    [135] Pryor W A, Prier D G, Chur D F. Electron-spin resonance study of mainstream and sidestream cigarette smoke: nature of the free radicals in gas-phase smoke and in cigarette tar[J]. Environmental Health Perspectives, 1983,47: 345-355
    [136] Johansson M, Fredholm L, Bjerna I, J(?)gerstad M. Influence of frying fat on the formation of heterocyclic amines in fried beefburgers and pan residues[J]. Food and Chemical Toxicology, 1995c, 33:993-1004
    [137] Kato T, Kikugawa K, Hayatsu H. Occurrence of the mutagens 2-amino-3,8- dimethylimidazo [4,5-f]-quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (4,8-MeIQx) in some Japanese smoked fish products[J]. Journal of Agriculture and Food Chemistry, 1986, 34: 810-814
    [138] Kikugawa K, Kato T, Hayatsu H. The presence of 2-amino-3, 8-dimethylimidazo [4, 5-f] quinoxaline in smoked dry bonito (katsuobushi) [J]. Japanese Journal of Cancer Research, 1986, 77:99-102
    [139] Holtz E, Skj61debrand C, J(?)gerstad M, et al. Effect of recipes on crust formation and mutagenicity in meat products during baking[J]. Journal of Food Technology, 1985,20: 57-66
    [140] Spingarn N E, Garvie-Gould C, Vuolo L L, et al. Formation of mutagens in cooked foodsⅣ. Effect of fat content in fried beef patties[J]. Cancer Letters, 1981,12: 93-97
    [141] Chen C, Pearson A M, Gray J I. Effect of fat content on mutagenicity of fried beef[J]. 35th ICoMST, Copenhagen, Denmark, 1989,436-439
    [142] Hayatsu H, Arimoto S, Togawa K, Makita M. Inhibitory effect of the ether extract of human feces on activities of mutagens: inhibition by oleic and linoleic acids[J]. Mutation Research, 1981,81:287-293
    [143] Arnoldi A, Arnoldi C, Baldi O, et al. Effect of lipids in the Maillard reaction[M]. In The Maillard Reaction. Advances in Life Sciences, ed. Finot P A, Aeschbacher H U, Hurrell R F, et al, Birkh(?)user Verlag, Basel. 1990,133-138
    [144] Barrington P J, Baker R S, Truswell A S, et al. Mutagenicity of basic fractions derived from lamb and beef cooked by common household methods[J]. Food and Chemical Toxicology, 1990, 28: 141-146
    [145] Wang Y Y, Vuolo L L, Spingarn N E, et al. Formation of mutagens in cooked foods. V. The mutagen reducing effect of soy protein concenrates and antioxidants during flying of beef[J]. Cancer Letters, 1982,16:179-189
    [146] Chen C, Pearson A M, Gray J I. Effects of synthetic antioxidants (BHA, BHT and PG) on the mutagenicity of IQ-like compounds[J]. Food Chemistry, 1992,43: 177-183
    [147] Pearson A M, Chen C, Gray J I. Effects of different antioxidants on formation of meat mutagens during frying of ground beef[J]. 38~(th) ICoMST. Clermont-Ferrad, France. 1992a, 567-570
    [148] Weisburger J H, Nagao M, Wakabayashi K, et al. Prevention of heterocyclic aromatic amine formation by tea and tea polyphenols[J]. Cancer Letter, 1994, 83:143-147
    [149] Kato T, Harashima T, Moriya N, et al. Formation of the mutagenoic/carcinogenic imidazoquinoxaline-type heterocyclic amines through the unstable free radical Maillard intermediates and its inhibition by phenolic antioxidants[J]. Carcinogenesis, 1996,11: 2469-2476
    [150] Oguri A, Suda M, Totsuka K, et al. Inhibitory effects of antioxidants on formation of heterocyclic amines[J]. Mutation Research, 1998, 402: 237-245
    [151] Murkovic M, Steinberger D, Pfannhauser W. Antioxidant spices reduce the formation of heterocyclic amines in fried meat[J]. Zeitschift fur Lebensmittel-Untersuchung und Forschung A, 1998,207:477-480
    [152] Bologh Z, Gray J I, Gomma E A, et al. Formation and inhibition of heterocyclic aromatic amines in fried ground beef patties[J]. Food and Chemical Toxicology, 2000, 38: 395-401
    [153] Salmon C P, Knize M G, Felton J S. Effects of marination on the of heterocyclic amine carcinogen formation in grilled chicken[J]. Food and Chemical Toxicology, 1997,35: 433-441
    [154] Nerurkar P V, Marchand L L, Cooney R V. Effect of marinating with Asian marinades or Western barbecue sauce on PhIP and MeIQx formation in barbecued beef[J]. Nutrition and cancer, 1999, 34:147-152
    [155] 李连弟，鲁凤珠，张思维等．中国恶性肿瘤死亡率20年变化趋势和近期预测分析[J]．中华肿瘤杂志，1997，19(1)：5-9
    [156] 韩弛，徐勇，施瑞丽等．中国传统加工食品致突变性的研究[J]．癌变·畸变·突变，1991，3(1)：8-12
    [157] 陈坤．结直肠癌环境与宿主因素的流行病学研究[D]，博士学位论文，浙江大学，2003．
    [1] Nagao M, Honda M, Seino Y, et al. Mutagenicities of smoke condensates and the charred surface of fish and meat[J].Cancer Letters, 1977,2: 221-226
    [2] Felton J S, Jagerstad M, Knize M G, et al. Contents in food, beverages and tobacco. In Food Borne Carcinogens: Heterocyclic Amines[C]//Nagao M, Sugimura T. John Wiley & Sons, Chichester, West Sussex, 2000: 31-72
    [3] Knize M, Gandresen B D, Healy S K, et al. Effects of temperature, patty thickness and fat content on the production of mutagens in fried ground beef[J]. Food and Chemical Toxicology, 1985, 23: 1035-1040
    [4] Knize M G, Dolbeare F A, Carroll K L, et al. Effect of cooking time and temperature on the heterocyclic amine content of fried beef patties[J]. Food and Chemical Toxicology, 1994, 32: 595-603
    [5] Stavric B. Biological significance of trace levels of mutagenic heterocyclic aromatic amines in human diet: a critical review[J]. Food and Chemical Toxicology, 1994, 32: 977-994
    [6] Skog K, Steineck G, Augustsson K, et al. Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues[J]. Carcinogenesis, 1995,16: 861-867
    [7] Skog K, Augustsson K, Steineck G, et al. Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues[J]. Food and Chemical Toxicology, 1997, 35: 555-565
    [8] Knize M G, Felton J S. Formation and human risk of carcinogenic heterocyclic amines from natural precursors in meat[J]. Nutrition Review, 2005, 63:158-165
    [9] Sugimura T. Nutrition and dietary carcinogens[J]. Carcinogenesis, 2000,21: 387-395
    [10] IARC, 1993. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. No. 56. Some Naturally Occurring Substances: Food Items and Constituents. Heterocyclic Aromatic Amines and Mycotoxins. International Agency for Research on Cancer, Lyon.
    [11] Gross G A, Gr(?)er A. Quantitation of mutagenic/carcinogenic heterocyclic amines in food products[J]. Journal of Chromatography, 1992, 592: 271-278
    [12] 韩弛，徐勇，施瑞丽，等．中国传统加工食品致突变性的研究[J]．癌变·畸变·突变，1991，3(1)：8-12
    [13] Solyakov A, Skog K. Screening for heterocyclic amines in chicken cooked in various ways[J]. Food and Chemical Toxicology, 2002,40:1205-1211
    [14] Salmon C P, Knize M G, Felton J S. Effect of marinating on heterocyclic amine carcinogen formation inn grilled chicken[J]. Food and Chemical Toxicology, 1997, 35: 433-441
    [15] Chen B H, Yang D J. An improved analytical method for determination of heterocyclic amines in chicken legs[J]. Chromatographia, 1998,48:223-230
    [16] Messner C, Murkovic M. Evaluation of a new model system for studying the formation of heterocyclic amines[J]. Journal of Chromatography B, 2004, 802:19-26
    [17] Borgen E, Solyakov A, Skog K. Effects of precursor composition and water on the formation of heterocyclic amines in meat model systems[J]. Food Chemistry, 2001,74:11-19
    [18] Solyakov A, Skog K. Screening for heterocyclic amines in chicken cooked in various ways[J]. Food and Chemical Toxicology, 2002,40: 1205-1211
    [19] Pais P, Salmon C P, Knize M G et al. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings[J]. Journal of Agricultural and Food Chemistry, 1999,47:1098-1108
    [20] Gross G A. Simple methods for quantifying mutagenic heterocyclic aromatic amines in food products[J]. Carcinogenesis, 1990,11:1597-1603
    [21] Toribio F, Galceran M T, Puignou L. Separation of heterocyclic aromatic amines in food products[J]. Journal of Chromatography B. Biomedical Sciences and Applications, 2000, 747 (1-2): 171-202
    [22] Wakabayashi K, Nagao M, Esumi H, et al. Food-derived mutagens and carcinogens[J]. Cancer Research, 1992, 52 (Suppl.): 2092s-2098s
    [23] Wu J, Lee H K, Wong M K, et al. Determination of carcinogenic heterocyclic amines in satay by liquid chromatography[J]. Environmental Monitoring and Assessment, 1997,44: 405-412
    [24] Sinha R, Knize M G, Salmon C P, et al. Heterocyclic amine content of pork products cooked by different methods and to varying degrees of doneness[J]. Food and Chemical Toxicology, 1998, 36:289-297
    [25] Sugimura T, Nagao M, Wakabayashi K. Metabolic aspects of the comutagenic action of norharman[J]. Advances in Experimental Medicine and Biology, 1982,136b: 1011-1025
    [26] Wakabayashi K, Sugimura T. Heterocyclic amines formed in the diet: Carcinogenicity and its modulation by dietary factors[J]. J. Nutr. Biochem., 1998, 9: 604-612
    [27] de Meester C. Genotoxic potential of beta-carbolines: a review[J]. Mutation Research, 1995, 339: 139-153
    [28] Kuhn W, Muller T, Grosse H, et al.. Elevated levels of harman and norharman in cerebrospinal fluid of parkinsonian patients[J]. Journal of Neural Transmission, 1996,103:1435-1440
    [1] Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today[J]. Journal of the National Cancer Institute, 1981,66:1191-1308
    [2] Norat T, Riboli E. Meat consumption and colorectal cancer: a review of epidemiologic evidence[J]. Nutrition Reviews, 2001,59 (2): 37-47
    [3] Sugimura T. Nutrition and dietary carcinogens[J]. Carcinogenesis, 2000,21: 387-395
    [4] Felton J S, Jagerstad M, Knize M G, et al. Contents in food, beverages and tobacco. In Food Borne Carcinogens: Heterocyclic Amines[C]//Nagao M, Sugimura T. John Wiley & Sons, Chichester, West Sussex, 2000: 31-72
    [5] Skog K I, Johansson M A, Jagerstad M I. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake[J]. Food and Chemical Toxicology, 1998,36:879-896
    [6] Tsuda M, Negishi C, Makino R, et al. Use of nitrite and hypochlorite treatments in determination of the contributions of IQ-type and non-IQ-type heterocyclic amines to the mutagenicities in crude pyrolyzed materials[J]. Mutation Research, 1985, 147: 335-341
    [7] Ames B N, McCann J, Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test[J]. Mutation Research, 1975,31: 347-364
    [8] Wu R W, Tucker J D, Sorensen K J, et al. Differential effect of acetyltransferase expression on the genotoxicity of heterocyclic amines in CHO cells[J]. Mutation Research, 1997, 390: 93-103
    [9] Adamson R H, Takayama S, Sugimura T, et al. Induction of hepatocellular carcinoma in nonhuman primates by the food mutagen 2-amino-3-methylimidazo-[4,5-f]quinoline[J].Environmental Health Perspectives, 1994,102: 190-193
    [10] Adamson R H, Thorgeirsson U P, Snyderwine E G, et al. Carcinogenicity of 2-amino-3-methylimidazo-[4,5-f]quinoline in nonhuman primates: induction of tumours in three macaques[J]. Japanese Journal of Cancer Research, 1990, 81:10-14
    [11] Ohgaki H, Takayama S, Sugimura T. Carcinogenicities of heterocyclic amines in cooked food[J]. Mutation Research, 1991, 259: 399-410
    [12] Wakabayashi K, Nagao M, Esumi H, et al. Food-derived mutagens and carcinogens[J]. Cancer Research, 1992, 52 (Suppl.): 2092s-2098s
    [13] NIEHS, 2005. Cancer causing agents, 11th ed. National Institute of Environmental Health Sciences, National Toxicology Program, US Department of Health and Human Services.
    [14] Nagao M. A new approach to risk estimation of food-borne carcinogens heterocyclic amines- based on molecular information[J]. Mutation Research, 1999,431: 3-12
    [15] 杨承忠．未来肉鸭业发展中的几个关键问题思考[J]．中国禽业导刊，2005，15：10-11
    [16] Solyakov A, Skog K. Screening for heterocyclic amines in chicken cooked in various ways[J]. Food and Chemical Toxicology, 2002,40:1205-1211
    [17] Sinha R, Rothman N, Brown E D, et al. High concentrations of the carcinogen 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine (PhIP) occur in chicken but are dependent on the cooking method[J]. Cancer Research, 1995, 55:4516-4519
    [18] Holder C L, Preece S W, Conway S C, et al. Quantification of heterocyclic amine carcinogens in cooked meats using isotope dilution liquid chromatography/atmospheric pressure chemical ionization tandem mass spectrometry[J]. Rapid Communications in Mass Spectrometry, 1997,11: 1667-1672
    [19] Knize M G, Salmon C P, Hopmans E C, et al. Analysis of foods for heterocyclic aromatic amine carcinogens by solid phase extraction and high-performance liquid chromatography[J]. Journal of Chromatography A, 1997,763:179-185
    [20] Salmon C P, Knize M G, Felton J S. Effects of marinating on heterocyclic amine carcinogen formation in grilled chicken[J]. Food and Chemical Toxicology, 1997, 35:433-441
    [21] Calvo C. Optical properties[M]. In: Nolett, L.M.L. (Ed.), Handbook of Food Analysis, Marcel Dekker, New York. 1996, 1: 139-162
    [22] Nagao M, Yahagi T, Honda M, et al. Demonstration of mutagenicity of aniline and otoluidine by Norharman[J]. Proceedings of the Japanese Academy, 1977,53B: 34-37
    [23] Nagao M, Yahagi T, Sugimura T. Differences in effects of Norharman with various classes of chemical mutagens and amounts of S-9[J]. Biochemical and Biophysical Research Communications, 1978 83,373-378
    [24] Sugimura T, Nagao M, Wakabayashi K. Metabolic aspects of the comutagenic action of Norharman[J]. Advances in Experimental Medicine and Biology, 1982,136b: 1011-1025
    [25] Totsuka Y, Ushiyama H, Ishihara J, et al. Quantification of the co-mutagenic beta-carbolines, Norharman and Harman, in cigarette smoke condensates and cooked foods[J]. Cancer Letters, 1999,143:139-143
    [26] de Meester C. Genotoxic potential of beta-carbolines: a review[J]. Mutation Research, 1995, 339: 139-153
    [27] Kuhn W, Muller T, Grosse H, Rommelspacher H. Elevated levels of Harman and Norharman in cerebrospinal fluid of parkinsonian patients[J]. Journal of Neural Transmission, 1996,103:1435-
    [28] Felton J S, Fultz E, Dolbeare F A, Knize M G. Reduction of heterocyclic amine mutagens/carcinogens in fried beef patties by microwave pretreatment[J]. Food and Chemical Toxicology, 1994,32:897-903
    [29] Chiu C P, Yang D Y, Chen B H. Formation of heterocyclic amines in cooked chicken legs[J] Journal of Food Protection, 1998, 61: 712-719
    [30] Matsumoto T, Yoshida D, Tomita H. Determination of mutagens, amino-alpha-carbolines in grilled foods and cigarette smoke condensate[J]. Cancer Letters, 1981,12:105-110
    [31] Richling E, Haring D, Herderich M, Schreier P. Determination of heterocyclic aromatic amines (HAA) in commercially available meat products and fish by high performance liquid chromatography electrospray tandem mass spectrometry (HPLC-ESIMS-MS)[J]. Chromatographia, 1998,48: 258-262
    [32] Skog K, Augustsson K, Steineck G, et al. Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues[J]. Food and Chemical Toxicology, 1997,35: 555-565
    [33] Pais P, Salmon C P, Knize M G, Felton J S. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats, and meat drippings[J]. Journal of Agricultural and Food Chemistry, 1999, 47:1098-1108
    [34] Krul C, Luiten-Schuite A, Baandagger R, et al. Application of a dynamic in vitro gastrointestinal tract model to study the availability of food mutagens, using heterocyclic aromatic amines as model compounds[J]. Food and Chemical Toxicology, 2000, 38: 783-792
    [35] Sinha R, Rothman N. Role of well-done, grilled red meat, heterocyclic amines (HCAs) in the etiology of human cancer[J]. Cancer Letters, 1999,143: 189-194
    [36] Brockstedt U, Pfau W. Formation of 2-amino - carbolines in pan-fried poultry and 32P-postlabelling analysis of DNA adducts[J]. Zeitschrift fur Lebensmittel-Untersuchung und-Forschung A, 1998, 207: 472-476
    [37] Augustsson K, Skog K, Jagerstad M, Steineck G. Assessment of the human exposure to heterocyclic amines[J]. Carcinogenesis, 1997,18:1931-1935
    [38] Augustsson K, Skog K, Jagerstad M, et al. Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population-based study[J]. Lancet, 1999, 353:703-707
    [39] Sinha R, Rothman N. Exposure assessment of heterocyclic amines (HCAs) in epidemiologic studies[J]. Mutation Research, 1997, 376: 195-202
    [1] Reynolds T. Chemistry of nonenzymic browning. Ⅰ. The reaction between aldoses and amines[J]. Adv. Food Res., 1963,12,1-52
    [2] Powrie W, Wu C, Rosin M, et al. Clastogenic and mutagenic activities of Maillard reaction model systems[J]. Journal of food science, 1981,46:1433-1438
    [3] Shibamoto T, Nishimura O, Mihara S, et al. Mutagenicity of products obtained from a maltolammonia browning model system[J]. Journal of Agricultural and Food Chemistry, 1981, 29: 643-646
    [4] Spingarn N E, Garvie C T. Formation of mutagens in sugar ammonia model systems[J]. Journal of Agricultural and Food Chemistry, 1979,27:1319-1321
    [5] Wei C I, Kitamura K, Shibamoto T. Mutagenicity of Maillard browning products obtained from a starch-glycine model system[J]. Food and chemical toxicology, 1981,19:749-751
    [6] Stavric B. Biological significance of trace levels of mutagenic heterocyclic aromatic amine in human diet: a critical review[J]. Food and chemical toxicology, 1994,32:977-994
    [7] Jagerstad M, Skog K, Arvidsson P, et al. Chemistry, formation and occurrence of genetoxic heterocyclic amines identified in model systems and cooked foods[J]. Zeitschrift fur Lebensmittelunter suchung und Forschung A.1998,207: 419-427
    [8] Pais P, Salmon C P, Knize M G, et al. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems, meats and meat drippings[J]. Journal of Agricultural and Food Chemistry, 1999, 47: 1098-1108
    [9] Vikse R, Joner P E. Mutagenicity, creatine and nutrient contents of pan fried meat form various animal species[J]. Acta Vet. Scand, 1993, 34:1-7
    [10] ISO 1442:1997(E). Meat and meat products－Determination of moisture content [M]. International Standard, second edition. 1996.
    [11] ISO 937-1978(E). Meat and meat products-Determination of nitrogen content (Reference) [M]. International Standard, first edition. 1978.
    [12] ISO 1443-1973(E). Meat and meat products-Determination of total fat content [M]. International Standard, first edition. 1973.
    [13] GB/T 5009.4-2003.食品中灰分的测定[M].中华人民共和国国家标准
    [14] Dubois M. A colorimetric method for determination of sugars and related substances[J]. Anal. Chem. 1956,28:350-356
    [15] Somogyi M. A new reagent for the determination of sugars[J]. J. Biol. Chem. 1945,9160: 62-68
    [16] Dunnett M, Harris R C, Orme C E. Reverse-phase ion-pair high-performance liquid chromatography of phosphocreatine, creatine and creatinine in equine muscle[J]. Scand J Clin Lab Invest, 1991,51:137-141
    [17] Karlsson A. porcine muscle fibres-biochemical and histo-chemical properties in relation to meat quality[D]. Doctoral thesis, 1993, Swedish university of agricultural sciences, Uppsala, Sweden ISBN 91-576-4697-X.
    [18] Lee H, Tsai S J. Detection of IQ-type mutagens in canned roasted eel[J]. Food and chemical toxicology, 1991,29: 517-522
    [19] Borgen E, Solyakov A, Skog K. Effects of precursor composition and water on the formation of heterocyclic amines in meat model systems[J]. Food Chemistry, 2001,74:11-19
    [20] Miller A. Processing-induced mutagens in muscle foods[J]. Food Technology, 1985,139: 75
    [21] Skog K I, Johansson M A, Jagerstad M I. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake[J]. Food and Chemical Toxicology, 1998,36:879-896
    [22] Overvik E, Kleman M, Berg I, et al. Influence of creatine, amino acids and water on the formation of mutagenic heterocyclic amines found in cooked meat[J]. Carcinogenesis, 1989, 10: 2293-2300.
    [23] Johansson M A E, Fay L B, Gross G A, et al. Influence of amino acids on the formation of mutagenic/carcinogenic heterocyclic amines in a model system[J]. Carcinogenesis, 1995, 16: 2553-2560
    [24] Felton J S, Knize M G Heterocyclic amine mutagens/carcinogens in foods[M]. In handbook of experimental pharmacology, Cooper, C S, Grover P L. Eds. Springer-Verlag, Berlin, 1990, 94: 471-502
    [25] Shioya M, Wakabayashi K, Sato, S, et al. Formation of a mutagen, 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP) in cooked beef, by heating a mixture containing creatinine, phenylalanine and glucose[J]. Mutation Research, 1987,191:133-138
    [26] Sugimura T, Nagao M, Wakabayashi K. Metabolic aspects of the comutagenic action of Norharman[J]. Advances in Experimental Medicine and Biology, 1982,136b: 1011-1025
    [27] Chen B H, Meng C N. Formation of heterocyclic amines in a model system during heating[J]. Journal of food protection, 1999,62:1445-1450
    [28] Nagao M, Sato S, Sugimura T. Mutagens produced by heating foods[M]. In Waller G R, Feather M S(ed.), The Maillard reaction in foods and nutrition. ACS Symposium Ser. 215, Washington, D.C. 1983, 521-536.
    [29] Abdulkarim B G, Smith J S. Heterocyclic amines in fresh and processed meat products[J]. Journal of Agricultural and Food Chemistry, 1998, 46:4680-4687
    [30] Sugimura T, Sato S. Mutagens/carcinogens in foods[J]. Canc er Res. (Suppl), 1983, 43: 2415-2421
    [31] Yoshida D, Matsumoto T, Okamoto S, et al. Formation of mutagens by heating foods and model systems[J]. Environ. Health Perspect, 1986,67: 55-58
    [32] Taylor R T, Fultz E, Knize M G, Felton J S. Formation of the fried ground-beef mutagens 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6 phenylimidazo [4,5-b]pyridine (PhIP) from L-phenylalanine (phe) +creatinine (cre) (or creatine)[J]. Environ. Mutat, 1987,9: 106-106
    [33] Skog K, Jagerstad M. Effects of monosaccharides and disaccharides on the formation of food mutagens in model systems[J]. Mutation Research, 1990,230:262-272
    [34] Skog K, Jagerstad M. Effect of glucose on the formation of PhIP in a model system[J]. Carcinogenesis, 1991,12: 2297-2300
    [35] Skog K, Jagerstad M, Reutersward L A. Inhibitory effect of carbohydrates on the formation of mutatens in fried beef patties[J]. Food and Chemical toxicology, 1992a, 30: 681-688
    [1] Tikkanen L M, Latva-Kala K J, Heinio R L. Effect of commercial marinades on the mutagenic activity, sensory quality and amount of heterocyclic amines in chicken grilled under different conditions[J]. Food and Chemical Toxicology, 1996, 34: 725-730
    [2] Stavric B, Lau B, Matula T I, et al. Heterocyclic aromatic amines content in pre-processed meat cuts produced in Canada[J]. Food and Chemical Toxicology, 1997, 35:199-206
    [3] Sinha R, Rothman N, Salmon C P, et al. Heterocyclic amines content in beef cooked by different methods to varying degrees of doneness and gravy made from meat drippings[J]. Food and Chemical Toxicology, 1998a, 36:279-287
    [4] Sinha R, Knize M, Salmon C P, et al. Heterocyclic amines content of pork products cooked by different methods and to varying degrees of doneness[J]. Food and Chemical Toxicology, 1998b, 36:289-297
    [5] Johansson M, Jagerstad M. Occurrence of mutagenic/carcinogenic Heterocyclic amines in meat and fish products, including pan residues, prepared under domestic conditions[J]. Carcinogenesis, 1994,15:1511-1518
    [6] Knize M G, Sinha R, Brown E D, et al. Heterocyclic amine content in restaurant-cooked hamburgers, steaks, ribs, and chicken[J]. Journal of Food Chemistry, 1998,46:4648-4651
    [7] Gerhardsson de Verdier M, Hagman U, Peters R K, et al. Meat, cooking methods and colorectal cancer: a case-referent study in Stockholm[J]. Int. J. Cancer, 1991,49: 520-525
    [8] Thomson B M, Lake R J, Cresser P J, et al. Estimated cancer risk from heterocyclic amines in cooked meat- a New Zealand perspective[J]. Proceed. Nutri. Soc. New Zealand. 1996,22
    [9] Wolk A, Gridley G, Niwa S, et al. International renal cell cancer study: VII. Role of diet[J]. Int. J. Cancer, 1996,65:67-73
    [10] Walfare M R, Cooper J, Bassendine M F, et al. Relationship between acetylator status, smoking, diet and colorectal cancer risk in the north-east of England[J]. Carcinogenesis, 1997, 7: 1351-1354
    [11] De Stefani E, Deneo-Pellegrini H, Mendilaharusu M, et al. Meat intake, heterocyclic amines and risk of colorectal cancer: a case- control study in Uruguay[J]. Int. J. Oncol, 1997a, 10: 573-580
    [12] De Stefani E, Ronco A, Mendilaharusu M, et al. Meat intake , heterocyclic amines and risk of breast cancer: a case- control study in Uruguay. Cancer Epidemiology, Biomarkers & Prevention, 1997b, 6:573-581
    [13] Jagerstad M, Skog K, Grivas S, Olsson K. Formation of heterocyclic amines using model system[J]. Mutation Research, 1991, 259: 219-233
    [14] Jackson L S, Hargraves W A. Effects of time and temperature on the formation of MeIQx and DiMeIQx in a model system containing threonine, glucose, and creatine[J]. Journal of Food Chemistry, 1995,43:1678-1683
    [15] Arvidsson P, Boekel V, Skog K, et al. Kinetics of formation of polar heterocyclic amines in a meat model system[J]. Journal of Food Science, 1997, 62: 911-916
    [16] Hallstrom B. Heat and mass transport in solid foods[M]. In: Throne S. (Ed.), Development in Food Preservation. Barking: Applied Science, 1983,61-94
    [17] Skog K. A review. Cooking procedure and food mutagens[J]. Food Chemistry, 1993, 31: 655-675
    [18] Johansson M, Laurent B, Gross A, et al. Influence of amino acids on the formation of mutagenic/carcinogenic heterocyclic amines in a model system[J]. Carcinogenesis, 1995a, 16:2253-2560
    [19] Johansson M, Fredholm L, Bjerne I, et al. Influence of frying fat on the formation of Heterocyclic Amines in fried beef burgers and pan residues[J]. Food and Chemical Toxicology, 1995b, 33: 993-1004
    [20] Pais P, Salmon C P, Knize M, et al. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heating model systems, meats, and meat drippings[J]. Journal of Agricultural and Food Chemistry, 1999,47: 1098-1108
    [21] Jagerstad M. Chemistry, formation and occurrence of genotoxic heterocyclic amines identified in model systems and cooked food[J]. Lebensmittel Unters Forsch A, 1998 207:419-427
    [22] Chiu C P, Chen B H. Stability of heterocyclic amines during heating[J]. Food chemistry, 2000, 592: 267-272
    [23] Jagerstad M. Creatine and maillard reaction products as precursors of mutagenic compounds formed in fried beef[M]. In: Labuza T P, Reineccius G A, Monnier V, Orien J, Bayens J (Eds), The Maillard Reaction in Foods and Health. The Royal Society of Chemistry, 1983, 506-518
    [24] Milic B L, Djilas S M, Canadanovic-Burnet., J M. synthesis of some heterocyclic aminoimida-zoazarenes. Food chemistry, 1993,46: 273-276
    [25] Arvidsson P, Boekel V, Skog K, Solyakov A, et al. Kinetics of heterocyclic amines in a meat juice model system[J]. Journal of Food Science, 1999,64:216-221
    [26] Dubois M. A colorimetric method for determination of sugars and related substances[J]. Anal. Chem. 1956, 28: 350-356
    [27] Somogyi M. A new reagent for the determination of sugars[J]. J. Biol. Chem. 1945,9160: 62-68
    [28] Dunnett M, Harris R C, Orme C E. Reverse-phase ion-pair high-performance liquid chromatography of phosphocreatine, creatine and creatinine in equine muscle[J]. Scand J Clin Lab Invest, 1991,51:137-141
    [29] Van Boekel M A J S. Statistical aspects of kinetic modeling for food science problems[J]. Journal of Food Science, 1996, 61:477-485,489
    [30] Balogh Z, Gray J I, Gomaa E, et al. Formation and inhibition of heterocyclic aromatic amines in fried ground beef patties[J]. Food and Chemical Toxicology, 2000, 38:395-401
    [31] Skog K, Augustsson G, Steineck G, et al. Polar and non-polar heterocyclic amines in cooked fish and meat products and their corresponding pan residues[J]. Food and Chemical Toxicology, 1997, 35:555-565
    [32] Grivas S, Nyhammar T, Olsson K, et al. Isolation and identification of the food mutagens IQ and MeIQx from a heated model system of creatinine, glyine and fructose[J]. Food chemistry, 1986, 20:127-136
    [33] Keating G A, Layton D W, Felton J S. Factors determining dietary intakes of heterocyclic amines in cooked foods[J]. Mutation Research, 1999,443:149-156
    [34] Nyhammar T. Studies on the Maillard reaction and its role in the formation of food mutagens[D]. PhD Thesis. Swedish University of Agricultural Sciences. Uppsala, Sweden, 1986
    [35] Hwang D K, Ngadi M. Kinetics of heterocyclic amines formation in the meat emulsion at different fat contents[J]. Lebensm.-Wiss.u.-Technol, 2002,35:600-606
    [36] van Boekel M A J S, Walstra P. Use of kinetics in studying heat-induced changes in foods[J]. Ch. 2 in IDF Monograph Heat-Induced Chanes in Milk, P.F. Fox (Ed.), International Dairy Federation special issue 9501,2nd ed., Brussels, 1995,22-50
    [37] Tinoco I Jr, Sauer K, Wang J C, et al. Physical chemistry: Principles and applications in biological sciences[M]. Practive-Hall, Inc. 2002,314-398,740
    [38] van Boekel M A J S. Effect of heating on Mailllard reactions in milk[J]. Food Chemistry, 1998, 62: 403-414
    [1] Jagerstad M, Laser-Reutersward A, Olsson R, et al. Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds: effects of various amino acids[J]. Food Chemistry, 1983a, 12: 255-264
    [2] International Agency for Research on Cancer, 1993. Monographs on the Evaluation of Carcinogenic Risk to Humans[J], Vol. 56. lARC, Lyon.
    [3] Ohgaki H, Kusama K, Matsukura N, et al. Carcinogenicity in mice of a mutagenic compound, 2-amino-3-methylimidazo[4,5-f]quinoline, from broiled sardine, cooked beef and beef extract[J]. Carcinogenesis, 1984,5: 921-924
    [4] Ghoshal A, Snyderwine E G Excretion of food-derived heterocyclic amine carcinogens into breast milk of lactating rats and formation of DNA adducts in the newborn[J]. Carcinogenesis, 1993, 14: 2199-2203
    [5] Layton D W, Bogen K T, Knize M G, et al. Cancer risk of heterocyclic amines in cooked foods: an analysis and implications for research[J]. Carcinogenesis, 1995,16: 39-52
    [6] Schiffman M I, Felton J S. Fried foods and risk of colon cancer[J]. (Letter to the Editor). American Journal of Epidemiology, 1990,131: 376-378
    [7] Willett W C, Stampfer M J, Colditz G A, et al. Relation of meat, fat and fiber intake to the risk of colon cancer in a prospective study among women[J]. New England Journal of Medicine, 1990, 323: 1664-1672
    [8] Bogen K T. Cancer potencies of heterocyclic amines found in cooked foods[J]. Food and Chemical Toxicology, 1994,32: 505-515
    [9] Skog K I, Johansson M A, Jagerstad M I. Carcinogenic heterocyclic amines in model systems and cooked foods: a review on formation, occurrence and intake[J]. Food and Chemical Toxicology, 1998, 36: 879-896
    [10] Knize M G, Andresen B D, Healy S K, et al. Effects of temperature, patty thickness and fat content on the production of mutagens in fried ground beef[J]. Food and Chemical Toxicology, 1985,23:1035-1040
    [11] Knize M G, Dolbeare F A, Carroll K L, et al. Effect of cooking time and temperature on the heterocyclic amine content of fried beef patties[J]. Food and Chemical Toxicology, 1994, 32: 595-603
    [12] Skog K, Steineck G, Augustsson K, Jagerstad, M. Effect of cooking temperature on the formation of heterocyclic amines in fried meat products and pan residues[J]. Carcinogenesis, 1995, 16: 861-867
    [13] Jagerstad M, Laser Reutersvard A, Oste R, et al. Creatinine and Maillard reaction products as precursors of mutagenic compounds formed in fried beef[M]. In: Waller, G., Feather, M. (Eds.), The Maillard Reaction in Foods and Nutrition. Washington, DC, 1983, 507-519
    [14] Pais P, Salmon C, Knize M, Felton J. Formation of mutagenic/carcinogenic heterocyclic amines in dry-heated model systems,meat and meat drippings[J]. Journal of Agricultural and Food Chemistry, 1999,47: 1098-1108
    [15] Jagerstad M, Laser-Reutersward A, Oste R, et al. Creatinine and Maillard reaction products as precursors of mutagenic compounds formed in fried beef[M]. In ACS Symposium Series.The Maillard Reaction in Foods and Nutrition, ed. G. R. Waller and M. S. Feather. American Chemical Society, Washington, DC, 1983b, 215: 507-519
    [16] Namiki M, Hayashi T. Formation of novel free radical products in an early stage of Maillard reaction[J]. Progress in Food and Nutrition Science, 1981, 5: 81-91
    [17] Milic B L, Djilas S M, Canadanovic-Brunet J M. Synthesis of some heterocyclic aminoimidazoazarenes[J]. Food Chemistry, 1993,46: 273-276
    [18] Kikugawa K. Involvement of free radicals in the formation of heterocyclic amines and prevention by antioxidants[J]. Cancer Letters, 1999, 143: 123-126
    [19] Pearson A M, Chen C, Gray JI, Aust S D. Mechanisms involved in meat mutagen formation and inhibition[J]. Free Radical Biol. Med., 1992,13:161-167
    [20] Johansson M. Jagerstad M. Occurrence of mutagenic/carcinogenic heterocyclic amines in meat and fish products, including pan residues, prepared under domestic conditions[J]. Carcinogenesis, 1994,15: 1511-1518
    [21] Wakabayashi K, Sugimura T. Heterocyclic amines formed in the diet: Carcinogenicity and its modulation by dietary factors[J]. J. Nutr. Biochem, 1998, 9:604-612
    [22] Weisburger J H, Nagao M, Wakabayashi K, et al. Prevention of heterocyclic amine formation by tea and tea polyphenols[J]. Cancer Letters, 1994, 83:143-147
    [23] Weisburger J H, Veliath E, Larios E, et al. Tea polyphenols inhibit the formation of mutagens during the cooking of meat[J]. Mutation Research, 2002,516:19-22
    [24] Oguri A, Suda M, Totsuka Y, et al. Inhibitory effects of antioxidants on formation of heterocyclic amines[J]. Mutation Research, 1998,402:237-245
    [25] Balogh Z, Gray J I, Gomaa E A, et al. Formation and inhibition of heterocyclic aromatic amines in fried ground beef patties[J]. Food and Chemical Toxicology, 2000, 38: 395-401
    [26] Kikugawa K, Hiramoto K, Koto T. Prevention of the formation of mutagenic and/or carcinogenic heterocyclic amines by food factors[J]. Biofactors, 2000,12:123-127
    [27] Ferraresi R, Troiano L, Roat E , et al. Essential requirement of reduced glutathione (GSH) for t he antioxidant effect of t he flavonoid quercetin[J]. Free Radical Research, 2005, 39:1249-1258
    [28] Hongpattarakere T, Johnson E A. Natural antimicrobial components isolated from yerba mate (Hex paraguariensis)[J]. Food Res. Inst. UW-Madison Annual Rep, 1999,11: 39-40
    [29] Passwater R A, Kandaswami C. Pyconogenol: The super protector nutrient[M]. New Canaan. CT: Keats Publishing. Inc. 1994.
    [30] Bagchi D, Krohn R L, Garg A, et al. Comparative in vitro and in vivo free radicals scavenging abilities of grape seed proanthocyanidins and selected antioxidants. FASEBJ, 1997,11: A582
    [31] Faulkner J. Mechanism of heterocyclic amine formation in fried ground beef-the role of oxidized lipid and the Maillard reaction[D]. PhD Dissertation, Michigan State University, East Lansing, MI. 1994
    [32] Tai C Y, Lee K H, Chen B H. Effect of various additives on the formation of heterocyclic amines in fried fish fibre[J]. Food chemistry, 2001,75:309-316
    [33] Kato T, Michikoshi K, Minowa Y I, et al. Mutagenicity of cooked hamburger is reduced by addition of onion to ground beef[J]. Mutation Research, 1998,420: 109-114
    [34] Jones R C, Weisburger J H. 1-tryptophan inhibits formation of mutagens during cooking of meat in laboratory animals[J]. Mutation Research, 1988,206: 343-349
    [35] Skog K, Jagerstad M, Reutersward L A. Inhibitory effect of carbohydrates on the formation of mutagens in fried beef patties[J]. Food and Chemical Toxicology, 1992, 30: 681-688
    [36] Salmon C P, Knize M G, Felton J S. Effect of marinating on heterocyclic amine carcinogen formation in grilled chicken[J]. Food and Chemical Toxicology, 1997,35:433-441
    [37] Britt C, Gomaa E A, Gray J I, et al. Influence of cherry tissue on lipid oxidation and heterocyclic aromatic amine formation in ground beef patties[J]. Journal of Agricultural and Food Chemistry, 1998,46:4891-4897
    [38] Murkovic M, Steinberger D, Pfannhauser W. Antioxidant spices reduce the formation of heterocyclic amines in fried meat[J]. Zeitschrift fur Lebensmittel Unter-suchung und Forschung A,1998,207: 477-480
    [39] Skog K. Cooking procedures and food mutagens: a literature review[J]. Food and Chemical Toxicology, 1993, 31: 655-675
    [40] Kato T, Harashima T, Moriya N, e al. Formation of the mutagenic/carcinogenic imidazoquinoxaline -type heterocyclic amines through the unstable free Maillard intermediates and its inhibition by phenolic antioxidants[J]. Carcinogenesis, 1996,17: 2469-2476
    [41] Kato T, Hiramoto K, Kikugawa K. Mutagenicity of cooked hamburger is reduced by addition of ascorbate and erythorbate to ground beef[J]. Journal of Health Science, 2000,46: 389-392