甲醛暴露所致工人早期遗传损伤的研究
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摘要
甲醛是一种极易挥发的有机化合物,无色且有强烈刺激性气味,是重要的化工原料和有机溶剂,广泛应用于制造各种粘合剂、树脂、油漆、合成纤维等工业产品,也常用作消毒剂和防腐剂。虽然甲醛是人体的一种天然代谢产物,但是直接的甲醛接触仍会对耳鼻喉等感官产生刺激作用,长期暴露更是会对人体产生慢性毒性,甚至会导致癌症的发生。国际癌症研究署于2004年将甲醛列为Ⅰ类致癌物(人类致癌物),认为有足够的证据表明高浓度甲醛能致鼻咽癌,并可能导致白血病。
作为世界上最大的甲醛生产国和消费国,随着使用量的激增,甲醛所带来的公共卫生问题也越来越严重。对甲醛暴露人群进行有效的生物监测以及早期遗传损伤的研究对于评价职业有害因素的影响有着重大意义,也能为制定相关职业病的预防控制措施提供依据。
甲醛来源广泛且代谢迅速,其产物难以作为评价内暴露的生物标志物,它能与人血清中的白蛋白作用,产生甲醛-白蛋白加合物(FA-HSA),该指标不仅灵敏而且特异性强,能够代表甲醛暴露人群的生物有效剂量。本研究选取215名人造密度板工厂的甲醛暴露工人作为研究对象,经知情同意后,选择有代表性的车间,使用NIOSH标准的高效液相色谱法进行空气中甲醛含量的检测,并对所有工人进行问卷调查,采集血样。结果显示,低甲醛暴露车间的平均空气甲醛含量为(0.58±0.20)mg/m3,工人平均血清FA-HSA水平为(69.22±15.37)pg/ml;高甲醛暴露车间的平均空气甲醛含量为(1.48±0.61)mg/m3,工人平均血清FA-HSA水平为(136.29±89.49)pg/ml。分析结果显示,高甲醛暴露车间的外暴露与内暴露水平均显著性高于低甲醛暴露车间(P<0.001),该结果亦与文献报导的一致,我们认为血清FA-HSA水平能够反映工人的个体甲醛暴露水平。
研究表明甲醛具有遗传毒性,不仅能够导致DNA单、双链的断裂,还能使生物大分子产生交联。碱性单细胞凝胶电泳实验作为一种灵敏度较高的方法,可以检测单细胞水平上的DNA损伤;改良的KCl-SDS沉淀法可以用来检测细胞内DNA与蛋白质的交联程度;胞质分裂阻滞法微核实验则能够用来评价细胞染色体的损伤情况。本研究以工人外周血淋巴细胞为研究材料,选取了CBMN‰、OTM与DPC三个指标来评价人群的DNA损伤情况,结果并未发现低、中、高三个暴露组间CBMN‰、OTM与DPC的显著性差异(P>0.05)。对数据进行Spearman相关分析与Logistic回归分析后我们可以看到,人群OTM、CBMN‰值均与甲醛暴露工龄呈显著正相关(P值分别为0.003和<0.001,rs值分别为0.239和0.339),暴露工龄大于4.4年个体的高OTM发生风险是工龄不足1.5年个体的5.5倍,Ptrend<0.001;暴露工龄大于4.4年个体的高CBMN‰发生风险是工龄不足1.5年个体的8倍之多,Ptrend<0.001。
综上所述,本研究通过对甲醛暴露工人的生物监测,验证了血清FA-HSA含量可以作为有效的内暴露指标评价职业性甲醛暴露工人的个体接触水平。而对工人外周血淋巴细胞DNA损伤分析的结果显示,甲醛所造成的工人的遗传物质损伤是有累积效应的,其损伤程度会随着甲醛暴露年限的升高而上升,外周血淋巴细胞微核率与彗星尾距可以作为评价职业性甲醛暴露累积暴露剂量的生物标志物。
Formaldehyde (FA) is a simple one-carbon molecule that can be rapidly metabolized. It is endogenously produced and also formed through the metabolism of many xenobiotic agents. Acute exposure to formaldehyde can cause irritation in many organs, while prolonged exposure can lead to chronic toxicity and even cancer. Formaldehyde was nominated for possible reclassification in the 12th‘Report on Carcinogens’based on the 2004 review by the International Agency for Research on Cancer, which concluded that there was sufficient evidence for the carcinogenicity of formaldehyde in humans.
The predominant use of formaldehyde is in the production of industrial resins (mainly urea-formaldehyde) that are used to manufacture products such as adhesives and binders for wood products, and it is also used as a chemical intermediate. China is the largest formaldehyde producer and consumer in the world. With the large amount of use, formaldehyde pollution increasingly impacts millions of people, and the adverse health effects are of escalating concern in Chinese society and require further investigation. The biomonitoring of FA exposed workers and the investigation of sensitive biomarkers is an important and useful method to evaluate the formaldehyde-induced heath effect.
Typical biological indices of exposure, such as levels of formaldehyde or its metabolites in blood or urine, have proven to be ineffective measures of exposure. Some researchers demonstrated that formaldehyde binds human serum albumin covalently, giving rise to a molecular adduct (FA-HSA) having the formaldehyde as hapten. The finding suggests that the humoral immune response to the adduct FA-HSA would provide a biological marker of formaldehyde exposure and of effective dose. In this research, we used 215 workers employed in two plywood industries as our object of study, all subjects were interviewed with questionnaire and blood samples were collected. Air sampling and formaldehyde analysis were performed through HPLC according to the National Institute for Occupational Safety and Health (NIOSH) method in selected workshops, and serum FA-HSA were detected among all workers. The average concentration of FA in the low FA exposed workshop (0.58±0.20 mg/m3) is much lower than in the high FA exposed workshop (1.48±0.61 mg/m3), and the average concentration of serum FA-HSA is (69.22±15.37) pg/ml and (136.29±89.49) pg/ml respectively. As the rising of air formaldehyde concentrations, the concentrations of FA-HSA in serum also increase.
Formaldehyde can cause cytogenetic damage in exposed workers. In this study, KCL-SDS assay and single cell gel electrophoresis were used to investigate DNA-protein crosslinks and DNA strand breaks in human peripheral blood lymphocytes, and cytokinesis-block micronucleus assay was used to detect chromosome damage. The results didn’t show any significant difference of cytogenetic damage among low-exposure, intermediate-exposure and high-exposure groups (P>0.05), but it did show a positive correlation between working years and CBMN‰(rs=0.339, P<0.001) and OTM (rs=0.239, P=0.003). The workers whose working years were longer than 4.4 years had a higher CBMN‰risk as well as a higher OTM risk compared to the workers whose working years were shorter than 1.5 years (Ptrend<0.001).
In summary, we selected 215 occupational FA exposed workers as our study object and investigate the association of FA exposure and cytogenetic damage in peripheral lymohocytes. The results suggested that FA-HSA in serum can be a biomarker of FA exposure and of effective dose. With the increase of working years, the DNA damage of the workers also increases. CBMN‰and OTM can be used as effect biomakers to evaluate the accumulation of cytogenetic damage caused by FA exposure.
作为世界上最大的甲醛生产国和消费国,随着使用量的激增,甲醛所带来的公共卫生问题也越来越严重。对甲醛暴露人群进行有效的生物监测以及早期遗传损伤的研究对于评价职业有害因素的影响有着重大意义,也能为制定相关职业病的预防控制措施提供依据。
甲醛来源广泛且代谢迅速,其产物难以作为评价内暴露的生物标志物,它能与人血清中的白蛋白作用,产生甲醛-白蛋白加合物(FA-HSA),该指标不仅灵敏而且特异性强,能够代表甲醛暴露人群的生物有效剂量。本研究选取215名人造密度板工厂的甲醛暴露工人作为研究对象,经知情同意后,选择有代表性的车间,使用NIOSH标准的高效液相色谱法进行空气中甲醛含量的检测,并对所有工人进行问卷调查,采集血样。结果显示,低甲醛暴露车间的平均空气甲醛含量为(0.58±0.20)mg/m3,工人平均血清FA-HSA水平为(69.22±15.37)pg/ml;高甲醛暴露车间的平均空气甲醛含量为(1.48±0.61)mg/m3,工人平均血清FA-HSA水平为(136.29±89.49)pg/ml。分析结果显示,高甲醛暴露车间的外暴露与内暴露水平均显著性高于低甲醛暴露车间(P<0.001),该结果亦与文献报导的一致,我们认为血清FA-HSA水平能够反映工人的个体甲醛暴露水平。
研究表明甲醛具有遗传毒性,不仅能够导致DNA单、双链的断裂,还能使生物大分子产生交联。碱性单细胞凝胶电泳实验作为一种灵敏度较高的方法,可以检测单细胞水平上的DNA损伤;改良的KCl-SDS沉淀法可以用来检测细胞内DNA与蛋白质的交联程度;胞质分裂阻滞法微核实验则能够用来评价细胞染色体的损伤情况。本研究以工人外周血淋巴细胞为研究材料,选取了CBMN‰、OTM与DPC三个指标来评价人群的DNA损伤情况,结果并未发现低、中、高三个暴露组间CBMN‰、OTM与DPC的显著性差异(P>0.05)。对数据进行Spearman相关分析与Logistic回归分析后我们可以看到,人群OTM、CBMN‰值均与甲醛暴露工龄呈显著正相关(P值分别为0.003和<0.001,rs值分别为0.239和0.339),暴露工龄大于4.4年个体的高OTM发生风险是工龄不足1.5年个体的5.5倍,Ptrend<0.001;暴露工龄大于4.4年个体的高CBMN‰发生风险是工龄不足1.5年个体的8倍之多,Ptrend<0.001。
综上所述,本研究通过对甲醛暴露工人的生物监测,验证了血清FA-HSA含量可以作为有效的内暴露指标评价职业性甲醛暴露工人的个体接触水平。而对工人外周血淋巴细胞DNA损伤分析的结果显示,甲醛所造成的工人的遗传物质损伤是有累积效应的,其损伤程度会随着甲醛暴露年限的升高而上升,外周血淋巴细胞微核率与彗星尾距可以作为评价职业性甲醛暴露累积暴露剂量的生物标志物。
Formaldehyde (FA) is a simple one-carbon molecule that can be rapidly metabolized. It is endogenously produced and also formed through the metabolism of many xenobiotic agents. Acute exposure to formaldehyde can cause irritation in many organs, while prolonged exposure can lead to chronic toxicity and even cancer. Formaldehyde was nominated for possible reclassification in the 12th‘Report on Carcinogens’based on the 2004 review by the International Agency for Research on Cancer, which concluded that there was sufficient evidence for the carcinogenicity of formaldehyde in humans.
The predominant use of formaldehyde is in the production of industrial resins (mainly urea-formaldehyde) that are used to manufacture products such as adhesives and binders for wood products, and it is also used as a chemical intermediate. China is the largest formaldehyde producer and consumer in the world. With the large amount of use, formaldehyde pollution increasingly impacts millions of people, and the adverse health effects are of escalating concern in Chinese society and require further investigation. The biomonitoring of FA exposed workers and the investigation of sensitive biomarkers is an important and useful method to evaluate the formaldehyde-induced heath effect.
Typical biological indices of exposure, such as levels of formaldehyde or its metabolites in blood or urine, have proven to be ineffective measures of exposure. Some researchers demonstrated that formaldehyde binds human serum albumin covalently, giving rise to a molecular adduct (FA-HSA) having the formaldehyde as hapten. The finding suggests that the humoral immune response to the adduct FA-HSA would provide a biological marker of formaldehyde exposure and of effective dose. In this research, we used 215 workers employed in two plywood industries as our object of study, all subjects were interviewed with questionnaire and blood samples were collected. Air sampling and formaldehyde analysis were performed through HPLC according to the National Institute for Occupational Safety and Health (NIOSH) method in selected workshops, and serum FA-HSA were detected among all workers. The average concentration of FA in the low FA exposed workshop (0.58±0.20 mg/m3) is much lower than in the high FA exposed workshop (1.48±0.61 mg/m3), and the average concentration of serum FA-HSA is (69.22±15.37) pg/ml and (136.29±89.49) pg/ml respectively. As the rising of air formaldehyde concentrations, the concentrations of FA-HSA in serum also increase.
Formaldehyde can cause cytogenetic damage in exposed workers. In this study, KCL-SDS assay and single cell gel electrophoresis were used to investigate DNA-protein crosslinks and DNA strand breaks in human peripheral blood lymphocytes, and cytokinesis-block micronucleus assay was used to detect chromosome damage. The results didn’t show any significant difference of cytogenetic damage among low-exposure, intermediate-exposure and high-exposure groups (P>0.05), but it did show a positive correlation between working years and CBMN‰(rs=0.339, P<0.001) and OTM (rs=0.239, P=0.003). The workers whose working years were longer than 4.4 years had a higher CBMN‰risk as well as a higher OTM risk compared to the workers whose working years were shorter than 1.5 years (Ptrend<0.001).
In summary, we selected 215 occupational FA exposed workers as our study object and investigate the association of FA exposure and cytogenetic damage in peripheral lymohocytes. The results suggested that FA-HSA in serum can be a biomarker of FA exposure and of effective dose. With the increase of working years, the DNA damage of the workers also increases. CBMN‰and OTM can be used as effect biomakers to evaluate the accumulation of cytogenetic damage caused by FA exposure.
引文
[1] International Agency for Research on Cancer. Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropan-2-ol. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 2006, 88: 39-325.
[2] National Toxicology Program. Final Report on Carcinogens Background Document for Formaldehyde. Rep Carcinog Backgr Doc, 2010.
[3] IPCS. Concise International Chemical Assessment Document: Formaldehyde. WHO: Geneva, 2002.
[4] Bizzari S. CEH Marketing Report: Formaldehyde. CA: SRI International, 2000.
[5] Occupational Safety and Health Administration. Occupational exposure to formaldehyde. OSHA Fact Sheet, 1996: 92-27.
[6] Li ZQ, Wang XD. The production, consumption and future of formaldehyde in China. Methanol and Formaldehyde 2006, 3: 29–35.
[7] Xiaojiang Tang, Yang Bai, Anh Duong, et al. Formaldehyde in China: Production, consumption, exposure levels, and health effects. Environ Int, 2009, 35(8): 1210-24.
[8] International Agency for Research on Cancer. IARC classifies formaldehyde as carcinogenic to humans. IARC Press Release on No.153, 2004.
[9]何凤生.中华职业医学.人民卫生出版社, 1999: 614-631.
[10] Ma TH, Harris MM. Review of the genotoxicity of formaldehyde. Mutat Res, 1998, 196: 37-59.
[11] Links JM, Kensler TW, Groopman JD. Biomarkers and mechanistic approaches in environmental epidemiology. Annu Rev Public Health, 1995, 16: 83-103.
[12] Thrasher JD, Wojdani A, Cheung G, et al. Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes. Arch Environ Health, 1987, 42(6): 347-350.
[13] Thrasher JD, Broughton A, Micevich P. Antibodies and immune profiles of individuals occupationally exposed to formaldehyde. Am J Ind Med, 1988, 14: 479-488.
[14] Thrasher JD, Broughton A, Madison R. Immune activation and autoantibodies inhuman with long-term inhalation exposure to formaldehyde. Arch Environ Health, 1990, 45(4): 217-223.
[15] Madison RE, Broughton A, Thrasher JD. Immunologic biomarkers associated with an acute exposure to exothermic byproducts of a urea-formaldehyde spill. Environ Health Perspect, 1991, 94: 219-223.
[16] E. Carraro, S. Gasparini, G. Gilli. Identification of a Chemical Marker of Environmental Exposure to Formaldehyde. Environmental Research, 1999, 80: 132-137.
[17] Mauro Pala BS, Donatella Ugolini MS, Marcello Ceppi MS, et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detection and Prevention, 2008, 32: 121–126.
[18] Anthony Suruda, Paul Schulte, Mark Boeniger, et al. Cytogenetic effects of formaldehyde exposure in students of mortuary science. Cancer Epidemiol Biomarkers Prev. 1993, 2(5): 453-60.
[19] Ying CJ, Yan WS, Zhao MY, et al. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class. Biomed Environ Sci, 1997, 10(4): 451-455.
[20] Orsière T, Sari-Minodier I, Iarmarcovai G, et al. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat Res, 2006, 605(1-2): 30-41.
[21] Costa S, Coelho P, Costa C, et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology 2008, 252(1-3): 40-48.
[22] Shoufang Jiang, Liqun Yu, Juan Cheng, et al. Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutat Res, 2010, 695: 9–15.
[23] C. Clifford Conaway, John Whysner, Lynne K, et al. Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation. Pharmacol Ther, 1996, 71: 29-55.
[24] J Shaham, Y Bomstein, R Gurvich, et al. DNA–protein crosslinks and p53 proteinexpression in relation to occupational exposure to formaldehyde. Occup Environ Med, 2003, 60: 403-409.
[25] Shaham J, Bomstein Y, Meltzer A, et al. DNA-protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies. Carcinogenesis, 1996, 17(1): 121-125.
[26] Shaham J, Bomstein Y, Melzer A, et al. DNA-Protein crosslinks and sister chromatid exchanges as biomarkers of exposure to formaldehyde. Int J Occup Environ Health 1997, 3(2): 95-104.
[27] Snyder RD, Van Houten B. Genotoxicity of formaldehyde and an evaluation of its effects on the DNA repair process in human diploid fibroblasts. Mutat Res, 1986, 165(1): 21-30.
[28] Liu Y, Li CM, Lu Z, et al. Studies on formation and repair of formaldehyde- damaged DNA by detection of DNA-protein crosslinks and DNA breaks. Front Biosci, 2006, 11: 991-997.
[29] Vock EH, Lutz WK, Ilinskaya O, et al. Discrimination between genotoxicity and cytotoxicity for the induction of DNA double-strand breaks in cells treated with aldehydes and diepoxides. Mutat Res, 1999, 441(1): 85-93.
[30] Demkowicz-Dobrzanski K, Castonguay A. Modulation by glutathione of DNA strand breaks induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone and its aldehyde metabolites in rat hepatocytes. Carcinogenesis, 1992, 13(8): 1447-1454.
[31] Cosma GN, Jamasbi R, Marchok AC. Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells. Mutat Res, 1998, 201(1): 161-168.
[32] National Institute for Occupational Safety and Health. Formaldehyde: Method 2016. NIOSH Method, 2003, 3: 5-7.
[33] Kleindienst TE, Corse EW , Blanchard FT. Evaluation of the performance of DNPH-coated silica gel and C18 cartridges in the measurement of formaldehyde in the presence and absence of ozone. Environmental Science & Technology, 1998, 32(1): 124-130.
[34] Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of lowlevels of DNA damage in individual cells. Exp Cell Res, 1988, 175(1): 184-91.
[35] National Industrial Chemicals Notification and Assessment Scheme. Formaldehyde, Priority Existing Chemical Assessment Report. NICNAS, 2006.
[36]张朝武,周宜开.现代卫生检验, 2005: 565-569.
[37] Luoping Zhang, Xiaojiang Tang, Nathaniel Rothman, et al. Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev, 2010, 19(1): 80–88.
[38] McKelvey-Martin VJ, Green MH, Schmezer P, et al. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res, 1993, 288(1): 47-63.
[39] Olive PL, Banáth JP. The comet assay: a method to measure DNA damage in individual cells. Nature Protocols, 2006, 1(1): 23-29.
[40]朱志良,庄志雄,黄钰等.单细胞凝胶电泳图像分析系统的研制及应用.中华劳动卫生职业病杂志, 2001, 19(3): 298-300.
[41] Olive PL, Banath JP, Durand RE. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the‘comet’assay. Radiat Res, 1990, 122(1): 86-94.
[42] Fenech M, Chang WP, Kirsch-Volders M, et al. Human Micronucleus project. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res, 2003, 534: 65-75.
[43] Michael Fenech. Cytokinesis-block micronucleus cytome assay. Nature Protocols, 2007, 2(5): 1084-1104.
[44] Tian Y, Ishikawa H, Piao FY, et al. Micronucleus assay of human lymphocytes: a comparison of cytokinesis-block and human capillary blood lymphocytes methods. J Occup Health, 2003, 45(6): 408-9.
[45] Zhitkovich A, Costa M. A simple, sensitive assay to detect DNA-protein crosslinks in intact cells and in vivo. Carcinogenesis 1992, 13(8): 1485-9.
[1] International Agency for Research on Cancer. Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropan-2-ol. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 2006, 88: 39-325.
[2] Links JM, Kensler TW, Groopman JD. Biomarkers and mechanistic approaches in environmental epidemiology. Annu Rev Public Health, 1995, 16: 83-103.
[3] Heck HD, Casanova Schmitz M, Dodd PB, et al. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CHO under controlled conditions. Am Ind Hyg Assoc, 1985, 46(1): 1-3.
[4] Casanova M, Heck Hd'A, Everitt JI, et al. Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxicol, 1988, 26(8): 715-716.
[5] C. Clifford Conaway, John Whysner, Lynne K, et al. Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation. Pharmacol Ther, 1996, 71: 29-55.
[6] Einbrodt HJ, Prajsnar D, Erpenbeck J. Formaldehyde and formic acid level in the blood andurine of people following previous exposition to formaldehyde. Zentralbl Arbeitsmed Arbeitsschutz Prophyl, 1976, 26(8): 154-158.
[7] Gonschling LM, Beaulieu HJ, Melvin WW. Monitoring of formic acid in urine of humansexposed to low levels of formaldehyde. Am Ind Hyg Assoc J, 1984, 45(1): 19 - 23.
[8] Boeniger MF. Formate in urine as a biological indicator of formaldehyde exposure: areview. Am Ind Hyg Assoc J, 1987, 48(1): 900-908.
[9] Agency for Toxic Substances and Disease Registry. Toxicological Profile for Formaldehyde. U.S. Department of Health and Human Services, ATSDR, 1999.
[10] National Toxicology Program. Final Report on Carcinogens Background Document for Formaldehyde. Rep Carcinog Backgr Doc, 2010.
[11] Heck H, Casanova M. The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity. Regul ToxicolPharmacol, 2004, 40(2): 92-106.
[12] Shin HS, Ahn HS, Lee BH. Determination of thiazolidine-4-carboxylates in urine by chloroformate derivatization and gas chromatography-electron impact mass spectrometry. J Mass Spectrom, 2007, 42(9): 1225-32.
[13] Li GY, Lee HY, Shin HS, et al. Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect, 2007, 115(10): 1460-6.
[14] Thrasher JD, Wojdani A, Cheung G, et al. Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes. Arch Environ Health, 1987, 42(6): 347-350.
[15] Thrasher JD, Broughton A, Micevich P. Antibodies and immune profiles of individuals occupationally exposed to formaldehyde. Am J Ind Med, 1988, 14: 479-488.
[16] Thrasher JD, Broughton A, Madison R. Immune activation and autoantibodies in human with long-term inhalation exposure to formaldehyde. Arch Environ Health, 1990, 45(4): 217-223.
[17] Madison RE, Broughton A, Thrasher JD. Immunologic biomarkers associated with an acute exposure to exothermic byproducts of a urea-formaldehyde spill. Environ Health Perspect, 1991, 94: 219-223.
[18] E. Carraro, S. Gasparini, G. Gilli. Identification of a Chemical Marker of Environmental Exposure to Formaldehyde. Environmental Research, 1999, 80: 132-137.
[19] Mauro Pala BS, Donatella Ugolini MS, Marcello Ceppi MS, et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detection and Prevention, 2008, 32: 121–126.
[20] Shaham J, Bomstein Y, Meltzer A, et al. DNA-protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies. Carcinogenesis, 1996, 17(1): 121-125.
[21] Shaham J, Bomstein Y, Melzer A, et al. DNA-protein crosslinks and sister chromatid exchanges as biomarkers of exposure to formaldehyde. Int J Occup Environ Health, 1997, 3(2): 95-104.
[22] J Shaham, Y Bomstein, R Gurvich, et al. DNA–protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde. Occup Environ Med, 2003, 60: 403-409.
[23] Mingyao Wang, Guang Cheng, Silvia Balbo, et al. Clear differences in levels of a formaldehyde-DNA adduct in leukocytes of smokers and nonsmokers. Cancer Res, 2009, 69(18): 7170-4.
[24] Fenech, M. The in vitro micronucleus technique. Mutat. Res, 2000, 455: 81–95.
[25] Costa S, Coelho P, Costa C, et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology, 2008, 252(1-3): 40-48.
[26] Orsière T, Sari-Minodier I, Iarmarcovai G, et al. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat Res, 2006, 605(1-2): 30-41.
[27] Shoufang Jiang, Liqun Yu, Juan Cheng, et al. Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutation Research, 2010, 695: 9–15.
[28] Monica Neri, Stefano Bonassi, Lisbeth E, et al. Children’s exposure to environmental pollutants and biomarkers of genetic damage I: overview and critical issues. Mutation Research, 2006, 612: 1–13.
[29] Monica Neri, Donatella Ugolini, Stefano Bonassi, et al. Children’s exposure to environmental pollutants and biomarkers of genetic damage II: results of a comprehensive literature search and meta-analysis. Mutation Research, 2006, 612: 14–39.
[30] Luoping Zhang, Xiaojiang Tang, Nathaniel Rothman, et al. Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev, 2010, 19(1): 80–88.
[31] McKelvey-Martin VJ, Green MH, Schmezer P, et al. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res, 1993, 288(1):47-63.
[32] He JL, Jin LF, Jin HY. Detection of cytogenetic effects in peripheral lymphocytes of students exposed to formaldehyde with cytokinesis-blocked micronucleus assay. Biomed Environ Sci, 1998, 11(1): 87-92.
[33] Judith Shaham, Rachel Gurvich, Zalman Kaufman. Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde. Mutation Research, 2002, 514: 115–123.
[34] Ku RH, Billings RE. Relationships between formaldehyde metabolism and toxicity and glutathione concentrations in isolated rat hepatocytes. Chem Biol Interact, 1984, 51(1): 25-36.
[35] Shirley Teng, Kristin Beard, Jalal Pourahmad, et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chemico-Biological Interactions, 2001: 130-132, 285-296.
[36] Sogut S, Songur A, Ozen OA, et al. Does the subacute (4-week) exposure to formaldehyde inhalation lead to oxidant/antioxidant imbalance in rat liver. Eur J Gen Med, 2004, 1(3): 26-32.
[37] Gurel A, Coskun O, Armutcu F, et al. Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies. J Chem Neuroanat, 2005, 29(3): 173-178.
[38] Gulec M, Songur A, Sahin S, et al. Antioxidant enzyme activities and lipid peroxidation products in heart tissue of subacute and subchronic formaldehyde- exposed rats: a preliminary study. Toxicol Ind Health 2006, 22(3): 117-124.
[39] Kum C, Kiral F, Sekkin S, et al. Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers. Exp Anim 2007, 56(1): 35-42.
[40] Bono R, Romanazzi V, Munnia A, et al. Malondialdehyde-deoxyguanosine adduct formation in workers of pathology wards: the role of air formaldehyde exposure. Chem Res Toxicol, 2010, 23(8): 1342-8.
[41] Li Q, Wang ZY, Inagaki H, et al. Evaluation of contact sensitivity to formaldehyde and tetramethylthiuram monosulfide using a modified lymphocyte transformation test. Toxicology, 1995, 104(1-3): 17-23.
[42] Gaylor DW, Lutz WK, Conolly RB. Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde. Toxicol Sci, 2004, 77(1): 158-64.
[43] Monticello TM, Swenberg JA, Gross EA, et al. Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res, 1996, 56(5): 1012-22.
[44] Hedberg JJ, Backlund M, Str?mberg P, et al. Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter. Pharmacogenetics, 2001, 11(9): 815-24.
[45]蒋守芳,于立群,冷曙光等.甲醛暴露工人XRCC1基因多态性与DNA损伤的关系研究.卫生研究, 2006, 35(6): 675-677.
[46] Kim WJ, Terada N, Nomura T, et al. Effect of formaldehyde on the expression of adhesion molecules in nasal microvascular endothelial cells: the role of formaldehyde in the pathogenesis of sick building syndrome. Clin Exp Allergy, 2002, 32(2): 287-295.
[47] Hester SD, Benavides GB, Yoon L, et al. Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium. Toxicology, 2003, 187(1): 13-24.
[2] National Toxicology Program. Final Report on Carcinogens Background Document for Formaldehyde. Rep Carcinog Backgr Doc, 2010.
[3] IPCS. Concise International Chemical Assessment Document: Formaldehyde. WHO: Geneva, 2002.
[4] Bizzari S. CEH Marketing Report: Formaldehyde. CA: SRI International, 2000.
[5] Occupational Safety and Health Administration. Occupational exposure to formaldehyde. OSHA Fact Sheet, 1996: 92-27.
[6] Li ZQ, Wang XD. The production, consumption and future of formaldehyde in China. Methanol and Formaldehyde 2006, 3: 29–35.
[7] Xiaojiang Tang, Yang Bai, Anh Duong, et al. Formaldehyde in China: Production, consumption, exposure levels, and health effects. Environ Int, 2009, 35(8): 1210-24.
[8] International Agency for Research on Cancer. IARC classifies formaldehyde as carcinogenic to humans. IARC Press Release on No.153, 2004.
[9]何凤生.中华职业医学.人民卫生出版社, 1999: 614-631.
[10] Ma TH, Harris MM. Review of the genotoxicity of formaldehyde. Mutat Res, 1998, 196: 37-59.
[11] Links JM, Kensler TW, Groopman JD. Biomarkers and mechanistic approaches in environmental epidemiology. Annu Rev Public Health, 1995, 16: 83-103.
[12] Thrasher JD, Wojdani A, Cheung G, et al. Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes. Arch Environ Health, 1987, 42(6): 347-350.
[13] Thrasher JD, Broughton A, Micevich P. Antibodies and immune profiles of individuals occupationally exposed to formaldehyde. Am J Ind Med, 1988, 14: 479-488.
[14] Thrasher JD, Broughton A, Madison R. Immune activation and autoantibodies inhuman with long-term inhalation exposure to formaldehyde. Arch Environ Health, 1990, 45(4): 217-223.
[15] Madison RE, Broughton A, Thrasher JD. Immunologic biomarkers associated with an acute exposure to exothermic byproducts of a urea-formaldehyde spill. Environ Health Perspect, 1991, 94: 219-223.
[16] E. Carraro, S. Gasparini, G. Gilli. Identification of a Chemical Marker of Environmental Exposure to Formaldehyde. Environmental Research, 1999, 80: 132-137.
[17] Mauro Pala BS, Donatella Ugolini MS, Marcello Ceppi MS, et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detection and Prevention, 2008, 32: 121–126.
[18] Anthony Suruda, Paul Schulte, Mark Boeniger, et al. Cytogenetic effects of formaldehyde exposure in students of mortuary science. Cancer Epidemiol Biomarkers Prev. 1993, 2(5): 453-60.
[19] Ying CJ, Yan WS, Zhao MY, et al. Micronuclei in nasal mucosa, oral mucosa and lymphocytes in students exposed to formaldehyde vapor in anatomy class. Biomed Environ Sci, 1997, 10(4): 451-455.
[20] Orsière T, Sari-Minodier I, Iarmarcovai G, et al. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat Res, 2006, 605(1-2): 30-41.
[21] Costa S, Coelho P, Costa C, et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology 2008, 252(1-3): 40-48.
[22] Shoufang Jiang, Liqun Yu, Juan Cheng, et al. Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutat Res, 2010, 695: 9–15.
[23] C. Clifford Conaway, John Whysner, Lynne K, et al. Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation. Pharmacol Ther, 1996, 71: 29-55.
[24] J Shaham, Y Bomstein, R Gurvich, et al. DNA–protein crosslinks and p53 proteinexpression in relation to occupational exposure to formaldehyde. Occup Environ Med, 2003, 60: 403-409.
[25] Shaham J, Bomstein Y, Meltzer A, et al. DNA-protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies. Carcinogenesis, 1996, 17(1): 121-125.
[26] Shaham J, Bomstein Y, Melzer A, et al. DNA-Protein crosslinks and sister chromatid exchanges as biomarkers of exposure to formaldehyde. Int J Occup Environ Health 1997, 3(2): 95-104.
[27] Snyder RD, Van Houten B. Genotoxicity of formaldehyde and an evaluation of its effects on the DNA repair process in human diploid fibroblasts. Mutat Res, 1986, 165(1): 21-30.
[28] Liu Y, Li CM, Lu Z, et al. Studies on formation and repair of formaldehyde- damaged DNA by detection of DNA-protein crosslinks and DNA breaks. Front Biosci, 2006, 11: 991-997.
[29] Vock EH, Lutz WK, Ilinskaya O, et al. Discrimination between genotoxicity and cytotoxicity for the induction of DNA double-strand breaks in cells treated with aldehydes and diepoxides. Mutat Res, 1999, 441(1): 85-93.
[30] Demkowicz-Dobrzanski K, Castonguay A. Modulation by glutathione of DNA strand breaks induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone and its aldehyde metabolites in rat hepatocytes. Carcinogenesis, 1992, 13(8): 1447-1454.
[31] Cosma GN, Jamasbi R, Marchok AC. Growth inhibition and DNA damage induced by benzo[a]pyrene and formaldehyde in primary cultures of rat tracheal epithelial cells. Mutat Res, 1998, 201(1): 161-168.
[32] National Institute for Occupational Safety and Health. Formaldehyde: Method 2016. NIOSH Method, 2003, 3: 5-7.
[33] Kleindienst TE, Corse EW , Blanchard FT. Evaluation of the performance of DNPH-coated silica gel and C18 cartridges in the measurement of formaldehyde in the presence and absence of ozone. Environmental Science & Technology, 1998, 32(1): 124-130.
[34] Singh NP, McCoy MT, Tice RR, et al. A simple technique for quantitation of lowlevels of DNA damage in individual cells. Exp Cell Res, 1988, 175(1): 184-91.
[35] National Industrial Chemicals Notification and Assessment Scheme. Formaldehyde, Priority Existing Chemical Assessment Report. NICNAS, 2006.
[36]张朝武,周宜开.现代卫生检验, 2005: 565-569.
[37] Luoping Zhang, Xiaojiang Tang, Nathaniel Rothman, et al. Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev, 2010, 19(1): 80–88.
[38] McKelvey-Martin VJ, Green MH, Schmezer P, et al. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res, 1993, 288(1): 47-63.
[39] Olive PL, Banáth JP. The comet assay: a method to measure DNA damage in individual cells. Nature Protocols, 2006, 1(1): 23-29.
[40]朱志良,庄志雄,黄钰等.单细胞凝胶电泳图像分析系统的研制及应用.中华劳动卫生职业病杂志, 2001, 19(3): 298-300.
[41] Olive PL, Banath JP, Durand RE. Heterogeneity in radiation-induced DNA damage and repair in tumor and normal cells measured using the‘comet’assay. Radiat Res, 1990, 122(1): 86-94.
[42] Fenech M, Chang WP, Kirsch-Volders M, et al. Human Micronucleus project. HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. Mutat Res, 2003, 534: 65-75.
[43] Michael Fenech. Cytokinesis-block micronucleus cytome assay. Nature Protocols, 2007, 2(5): 1084-1104.
[44] Tian Y, Ishikawa H, Piao FY, et al. Micronucleus assay of human lymphocytes: a comparison of cytokinesis-block and human capillary blood lymphocytes methods. J Occup Health, 2003, 45(6): 408-9.
[45] Zhitkovich A, Costa M. A simple, sensitive assay to detect DNA-protein crosslinks in intact cells and in vivo. Carcinogenesis 1992, 13(8): 1485-9.
[1] International Agency for Research on Cancer. Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropan-2-ol. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, 2006, 88: 39-325.
[2] Links JM, Kensler TW, Groopman JD. Biomarkers and mechanistic approaches in environmental epidemiology. Annu Rev Public Health, 1995, 16: 83-103.
[3] Heck HD, Casanova Schmitz M, Dodd PB, et al. Formaldehyde (CH2O) concentrations in the blood of humans and Fischer-344 rats exposed to CHO under controlled conditions. Am Ind Hyg Assoc, 1985, 46(1): 1-3.
[4] Casanova M, Heck Hd'A, Everitt JI, et al. Formaldehyde concentrations in the blood of rhesus monkeys after inhalation exposure. Food Chem Toxicol, 1988, 26(8): 715-716.
[5] C. Clifford Conaway, John Whysner, Lynne K, et al. Formaldehyde mechanistic data and risk assessment: endogenous protection from DNA adduct formation. Pharmacol Ther, 1996, 71: 29-55.
[6] Einbrodt HJ, Prajsnar D, Erpenbeck J. Formaldehyde and formic acid level in the blood andurine of people following previous exposition to formaldehyde. Zentralbl Arbeitsmed Arbeitsschutz Prophyl, 1976, 26(8): 154-158.
[7] Gonschling LM, Beaulieu HJ, Melvin WW. Monitoring of formic acid in urine of humansexposed to low levels of formaldehyde. Am Ind Hyg Assoc J, 1984, 45(1): 19 - 23.
[8] Boeniger MF. Formate in urine as a biological indicator of formaldehyde exposure: areview. Am Ind Hyg Assoc J, 1987, 48(1): 900-908.
[9] Agency for Toxic Substances and Disease Registry. Toxicological Profile for Formaldehyde. U.S. Department of Health and Human Services, ATSDR, 1999.
[10] National Toxicology Program. Final Report on Carcinogens Background Document for Formaldehyde. Rep Carcinog Backgr Doc, 2010.
[11] Heck H, Casanova M. The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity. Regul ToxicolPharmacol, 2004, 40(2): 92-106.
[12] Shin HS, Ahn HS, Lee BH. Determination of thiazolidine-4-carboxylates in urine by chloroformate derivatization and gas chromatography-electron impact mass spectrometry. J Mass Spectrom, 2007, 42(9): 1225-32.
[13] Li GY, Lee HY, Shin HS, et al. Identification of gene markers for formaldehyde exposure in humans. Environ Health Perspect, 2007, 115(10): 1460-6.
[14] Thrasher JD, Wojdani A, Cheung G, et al. Evidence for formaldehyde antibodies and altered cellular immunity in subjects exposed to formaldehyde in mobile homes. Arch Environ Health, 1987, 42(6): 347-350.
[15] Thrasher JD, Broughton A, Micevich P. Antibodies and immune profiles of individuals occupationally exposed to formaldehyde. Am J Ind Med, 1988, 14: 479-488.
[16] Thrasher JD, Broughton A, Madison R. Immune activation and autoantibodies in human with long-term inhalation exposure to formaldehyde. Arch Environ Health, 1990, 45(4): 217-223.
[17] Madison RE, Broughton A, Thrasher JD. Immunologic biomarkers associated with an acute exposure to exothermic byproducts of a urea-formaldehyde spill. Environ Health Perspect, 1991, 94: 219-223.
[18] E. Carraro, S. Gasparini, G. Gilli. Identification of a Chemical Marker of Environmental Exposure to Formaldehyde. Environmental Research, 1999, 80: 132-137.
[19] Mauro Pala BS, Donatella Ugolini MS, Marcello Ceppi MS, et al. Occupational exposure to formaldehyde and biological monitoring of Research Institute workers. Cancer Detection and Prevention, 2008, 32: 121–126.
[20] Shaham J, Bomstein Y, Meltzer A, et al. DNA-protein crosslinks, a biomarker of exposure to formaldehyde--in vitro and in vivo studies. Carcinogenesis, 1996, 17(1): 121-125.
[21] Shaham J, Bomstein Y, Melzer A, et al. DNA-protein crosslinks and sister chromatid exchanges as biomarkers of exposure to formaldehyde. Int J Occup Environ Health, 1997, 3(2): 95-104.
[22] J Shaham, Y Bomstein, R Gurvich, et al. DNA–protein crosslinks and p53 protein expression in relation to occupational exposure to formaldehyde. Occup Environ Med, 2003, 60: 403-409.
[23] Mingyao Wang, Guang Cheng, Silvia Balbo, et al. Clear differences in levels of a formaldehyde-DNA adduct in leukocytes of smokers and nonsmokers. Cancer Res, 2009, 69(18): 7170-4.
[24] Fenech, M. The in vitro micronucleus technique. Mutat. Res, 2000, 455: 81–95.
[25] Costa S, Coelho P, Costa C, et al. Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde. Toxicology, 2008, 252(1-3): 40-48.
[26] Orsière T, Sari-Minodier I, Iarmarcovai G, et al. Genotoxic risk assessment of pathology and anatomy laboratory workers exposed to formaldehyde by use of personal air sampling and analysis of DNA damage in peripheral lymphocytes. Mutat Res, 2006, 605(1-2): 30-41.
[27] Shoufang Jiang, Liqun Yu, Juan Cheng, et al. Genomic damages in peripheral blood lymphocytes and association with polymorphisms of three glutathione S-transferases in workers exposed to formaldehyde. Mutation Research, 2010, 695: 9–15.
[28] Monica Neri, Stefano Bonassi, Lisbeth E, et al. Children’s exposure to environmental pollutants and biomarkers of genetic damage I: overview and critical issues. Mutation Research, 2006, 612: 1–13.
[29] Monica Neri, Donatella Ugolini, Stefano Bonassi, et al. Children’s exposure to environmental pollutants and biomarkers of genetic damage II: results of a comprehensive literature search and meta-analysis. Mutation Research, 2006, 612: 14–39.
[30] Luoping Zhang, Xiaojiang Tang, Nathaniel Rothman, et al. Occupational exposure to formaldehyde, hematotoxicity and leukemia-specific chromosome changes in cultured myeloid progenitor cells. Cancer Epidemiol Biomarkers Prev, 2010, 19(1): 80–88.
[31] McKelvey-Martin VJ, Green MH, Schmezer P, et al. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res, 1993, 288(1):47-63.
[32] He JL, Jin LF, Jin HY. Detection of cytogenetic effects in peripheral lymphocytes of students exposed to formaldehyde with cytokinesis-blocked micronucleus assay. Biomed Environ Sci, 1998, 11(1): 87-92.
[33] Judith Shaham, Rachel Gurvich, Zalman Kaufman. Sister chromatid exchange in pathology staff occupationally exposed to formaldehyde. Mutation Research, 2002, 514: 115–123.
[34] Ku RH, Billings RE. Relationships between formaldehyde metabolism and toxicity and glutathione concentrations in isolated rat hepatocytes. Chem Biol Interact, 1984, 51(1): 25-36.
[35] Shirley Teng, Kristin Beard, Jalal Pourahmad, et al. The formaldehyde metabolic detoxification enzyme systems and molecular cytotoxic mechanism in isolated rat hepatocytes. Chemico-Biological Interactions, 2001: 130-132, 285-296.
[36] Sogut S, Songur A, Ozen OA, et al. Does the subacute (4-week) exposure to formaldehyde inhalation lead to oxidant/antioxidant imbalance in rat liver. Eur J Gen Med, 2004, 1(3): 26-32.
[37] Gurel A, Coskun O, Armutcu F, et al. Vitamin E against oxidative damage caused by formaldehyde in frontal cortex and hippocampus: biochemical and histological studies. J Chem Neuroanat, 2005, 29(3): 173-178.
[38] Gulec M, Songur A, Sahin S, et al. Antioxidant enzyme activities and lipid peroxidation products in heart tissue of subacute and subchronic formaldehyde- exposed rats: a preliminary study. Toxicol Ind Health 2006, 22(3): 117-124.
[39] Kum C, Kiral F, Sekkin S, et al. Effects of xylene and formaldehyde inhalations on oxidative stress in adult and developing rats livers. Exp Anim 2007, 56(1): 35-42.
[40] Bono R, Romanazzi V, Munnia A, et al. Malondialdehyde-deoxyguanosine adduct formation in workers of pathology wards: the role of air formaldehyde exposure. Chem Res Toxicol, 2010, 23(8): 1342-8.
[41] Li Q, Wang ZY, Inagaki H, et al. Evaluation of contact sensitivity to formaldehyde and tetramethylthiuram monosulfide using a modified lymphocyte transformation test. Toxicology, 1995, 104(1-3): 17-23.
[42] Gaylor DW, Lutz WK, Conolly RB. Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde. Toxicol Sci, 2004, 77(1): 158-64.
[43] Monticello TM, Swenberg JA, Gross EA, et al. Correlation of regional and nonlinear formaldehyde-induced nasal cancer with proliferating populations of cells. Cancer Res, 1996, 56(5): 1012-22.
[44] Hedberg JJ, Backlund M, Str?mberg P, et al. Functional polymorphism in the alcohol dehydrogenase 3 (ADH3) promoter. Pharmacogenetics, 2001, 11(9): 815-24.
[45]蒋守芳,于立群,冷曙光等.甲醛暴露工人XRCC1基因多态性与DNA损伤的关系研究.卫生研究, 2006, 35(6): 675-677.
[46] Kim WJ, Terada N, Nomura T, et al. Effect of formaldehyde on the expression of adhesion molecules in nasal microvascular endothelial cells: the role of formaldehyde in the pathogenesis of sick building syndrome. Clin Exp Allergy, 2002, 32(2): 287-295.
[47] Hester SD, Benavides GB, Yoon L, et al. Formaldehyde-induced gene expression in F344 rat nasal respiratory epithelium. Toxicology, 2003, 187(1): 13-24.
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