基于斑马鱼毒理基因组学的化学品测试技术研究进展
|
摘要
大量缺乏毒性信息的化学品最终进入环境水体,对人类及生态生物产生潜在的危害与风险。提高化学品生物毒性测试与评估技术的通量和效率,是实现毒害化学物质环境与生态健康风险防控的关键。作为一种可以实现高通量测试的脊椎动物模型,斑马鱼胚胎测试在化学品的毒性评估中应用广泛。随着组学技术的发展,毒理基因组学可有效提取毒害化学品致毒过程中干扰生物学通路的信息。这些机制信息可用于对单物质或复合污染物生物毒性的筛选和预测。本文综述了不同斑马鱼胚胎测试技术在化学品毒性筛选评估管理与水环境复合污染毒性监测中的发展和应用,详细介绍了一种新型斑马鱼胚胎简化转录组学技术的方法流程和优势,并探讨了综合斑马鱼胚胎毒性测试、行为分析和组学等不同测试技术在化学品毒性测试、环境监测与评价中的应用前景。
Numerous synthetic chemicals have been produced for industrial,domestic or agricultural use without thorough toxicological assessment.These synthetic chemicals finally enter aquatic environment through anthropogenic activities and pose health risk to human and aquatic ecosystem.Globally an urgent demand has been recognized to develop new approaches that allow high throughput toxicity testing and risk assessment of chemicals.The zebrafish embryo model has been widely used in toxicological evaluation of chemicals;however,the current approaches generally lack of mechanism knowledge.With the advances of the omics technology,it is possible to uncoverthe molecular information on disrupted biological pathways in the process of chemicals-induced toxicity,in a high throughput manner.The molecular information can be used to screen and predict the biological toxicity of chemicals or chemical mixtures.Here,we reviewed the major advances of zebrafish embryo testing methodologies in chemical testing and risk assessment of chemical mixtures,which included high content screening,locomotor behavior test.Secondly,we introduced a novel zebrafish toxicogenomic approaches named Reduced Zebrafish Transcriptome(RZT) for high throughput chemical testing.The future application of an aggregate zebrafish toxicology testing methods,including RZT,in chemical toxicity evaluation and water environment monitoring was discussed.
Numerous synthetic chemicals have been produced for industrial,domestic or agricultural use without thorough toxicological assessment.These synthetic chemicals finally enter aquatic environment through anthropogenic activities and pose health risk to human and aquatic ecosystem.Globally an urgent demand has been recognized to develop new approaches that allow high throughput toxicity testing and risk assessment of chemicals.The zebrafish embryo model has been widely used in toxicological evaluation of chemicals;however,the current approaches generally lack of mechanism knowledge.With the advances of the omics technology,it is possible to uncoverthe molecular information on disrupted biological pathways in the process of chemicals-induced toxicity,in a high throughput manner.The molecular information can be used to screen and predict the biological toxicity of chemicals or chemical mixtures.Here,we reviewed the major advances of zebrafish embryo testing methodologies in chemical testing and risk assessment of chemical mixtures,which included high content screening,locomotor behavior test.Secondly,we introduced a novel zebrafish toxicogenomic approaches named Reduced Zebrafish Transcriptome(RZT) for high throughput chemical testing.The future application of an aggregate zebrafish toxicology testing methods,including RZT,in chemical toxicity evaluation and water environment monitoring was discussed.
引文
[1]Hartung T.Toxicology for the twenty-first century[J].Nature,2009,460(7252):208-212
[2]Judson R,Richard A,Dix D J,et al.The toxicity data landscape for environmental chemicals[J].Environmental Health Perspectives,2009,117(5):685-695
[3]刘辉,戴家银.斑马鱼在生态毒理学研究及环境监测中的应用[J].中国实验动物学报,2015,23(5):529-534Liu H,Dai J Y.Application of zebrafish(Danio rerio)in the fields of environmental ecotoxicology and environmental monitoring[J].Acta Laboratorium Animals Scientia Sinica,2015,23(5):529-534(in Chinese)
[4]Zhang X,Xia P,Wang P,et al.Omics advances in ecotoxicology[J].Environmental Science&Technology,2018,52(7):3842-3851
[5]Collins F S,Gray G M,Bucher J R.Transforming environmental health protection[J].Science,2008,319(5865):906-907
[6]Schwarzenbach R P,Escher B I,Fenner K,et al.The challenge of micropollutants in aquatic systems[J].Science,2006,313(5790):1072-1077
[7]Altenburger R,Ait-Aissa S,Antczak P,et al.Future water quality monitoring-Adapting tools to deal with mixtures of pollutants in water resource management[J].Science of The Total Environment,2015,512-513:540-551
[8]Kavlock R,Chandler K,Houck K,et al.Update on EPA's Tox Cast program:Providing high throughput decision support tools for chemical risk management[J].Chemical Research in Toxicology,2012,25(7):1287-1302
[9]Brack W,Schmitt-Jansen M,Machala M,et al.How to confirm identified toxicants in effect-directed analysis[J].Analytical and Bioanalytical Chemistry,2008,390(8):1959-1973
[10]Connon R E,Geist J,Werner I.Effect-based tools for monitoring and predicting the ecotoxicological effects of chemicals in the aquatic environment[J].Sensors,2012,12(9):12741-12771
[11]Li H,Zhang J,You J.Diagnosis of complex mixture toxicity in sediments:Application of toxicity identification evaluation(TIE)and effect-directed analysis(EDA)[J].Environmental Pollution,2017,237:944-954
[12]de Esch C,Slieker R,Wolterbeek A,et al.Zebrafish as potential model for developmental neurotoxicity testing:A mini review[J].Neurotoxicology and Teratology,2012,34(6):545-553
[13]Sipes N S,Padilla S,Knudsen T B.Zebrafish:As an integrative model for twenty-first century toxicity testing[J].Birth Defects Research Part C:Embryo Today:Reviews,2011,93(3):256-267
[14]Sobanska M,Scholz S,Nyman A M,et al.Applicability of the fish embryo acute toxicity(FET)test(OECD236)in the regulatory context of Registration,Evaluation,Authorisation,and Restriction of Chemicals(REACH)[J].Environmental Toxicology and Chemistry,2018,37(3):657-670
[15]Di Paolo C,Seiler T-B,Keiter S,et al.The value of zebrafish as an integrative model in effect-directed analysis-A review[J].Environmental Sciences Europe,2015,27(1):8-19
[16]McCollum C W,Ducharme N A,Bondesson M,et al.Developmental toxicity screening in zebrafish[J].Birth Defects Research Part C:Embryo Today:Reviews,2011,93(2):67-114
[17]Hallare A,Nagel K,Kohler H R,et al.Comparative embryotoxicity and proteotoxicity of three carrier solvents to zebrafish(Danio rerio)embryos[J].Ecotoxicology and Environmental Safety,2006,63(3):378-388
[18]Noyes P D,Garcia G R,Tanguay R L.Zebrafish as an in vivo model for sustainable chemical design[J].Green Chemistry,2016,18(24):6410-6430
[19]Mandrell D,Truong L,Jephson C,et al.Automated zebrafish chorion removal and single embryo placement:Optimizing throughput of zebrafish developmental toxicity screens[J].Journal of Laboratory Automation,2012,17(1):66-74
[20]Yozzo K L,Isales G M,Raftery T D,et al.High-content screening assay for identification of chemicals impacting cardiovascular function in zebrafish embryos[J].Environmental Science&Technology,2013,47(19):11302-11310
[21]Padilla S,Corum D,Padnos B,et al.Zebrafish developmental screening of the Tox Cast Phase I chemical library[J].Reprodutive Toxicology,2012,33(2):174-187
[22]Reif D M,Truong L,Mandrell D,et al.High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes[J].Archives of Toxicology,2016,90(6):1459-1470
[23]Truong L,Reif D M,St Mary L,et al.Multidimensional in vivo hazard assessment using zebrafish[J].Toxicological Sciences,2014,137(1):212-233
[24]Zhang G,Truong L,Tanguay R L,et al.A new statistical approach to characterize chemical-elicited behavioral effects in high-throughput studies using zebrafish[J].PLoS One,2017,12(1):e0169408
[25]Kokel D,Dunn T W,Ahrens M B,et al.Identification of nonvisual photomotor response cells in the vertebrate hindbrain[J].The Journal of Neuroscience,2013,33(9):3834-3843
[26]Tierney K B.Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish[J].Biochimica Biophysica Acta,2011,1812(3):381-389
[27]Bruni G,Rennekamp A J,Velenich A,et al.Zebrafish behavioral profiling identifies multitarget antipsychoticlike compounds[J].Nature Chemical Biology,2016,12(7):559-566
[28]Kokel D,Bryan J,Laggner C,et al.Rapid behavior-based identification of neuroactive small molecules in the zebrafish[J].Nature Chemical Biology,2010,6(3):231-237
[29]Noyes P D,Haggard D E,Gonnerman G D,et al.Advanced morphological-behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants[J].Toxicological Sciences,2015,145(1):177-195
[30]Kluver N,Konig M,Ortmann J,et al.Fish embryo toxicity test:Identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds[J].Environmental Science&Technology,2015,49(11):7002-7011
[31]Zhang K,Zhao Y,Fent K,et al.Occurrence and ecotoxicological effects of free,conjugated,and halogenated steroids including 17alpha-hydroxypregnanolone and pregnanediol in Swiss wastewater and surface water[J].Environmental Science&Technology,2017,51(11):6498-6506
[32]Chen M,Zhang M,Borlak J,et al.A decade of toxicogenomic research and its contribution to toxicological science[J].Toxicological Sciences,2012,130(2):217-228
[33]Simmons D B,Benskin J P,Cosgrove J R,et al.Omics for aquatic ecotoxicology:Control of extraneous variability to enhance the analysis of environmental effects[J].Environmental Toxicology and Chemistry,2015,34(8):1693-1704
[34]Yan S-K,Liu R-H,Jin H-Z,et al.“Omics”in pharmaceutical research:Overview,applications,challenges,and future perspectives[J].Chinese Journal of Natural Medicines,2015,13(1):3-21
[35]Antczak P,Jo H J,Woo S,et al.Molecular toxicity identification evaluation(m TIE)approach predicts chemical exposure in Daphnia magna[J].Environmental Science&Technology,2013,47(20):11747-11756
[36]Schaap M M,Wackers P F,Zwart E P,et al.A novel toxicogenomics-based approach to categorize(non-)genotoxic carcinogens[J].Archives of Toxicology,2015,89(12):2413-2427
[37]Peng Y,Xia P,Zhang J,et al.Toxicogenomic assessment of 6-OH-BDE47-induced developmental toxicity in chicken embryos[J].Environmental Science&Technology,2016,50(22):12493-12503
[38]陆韻,侯凌燕,胡洪营,等.毒理基因组学研究进展[J].生态环境学报,2010,19(9):2232-2239Lu X,Hou L Y,Hu H Y,et al.Progress in toxicogenomics[J].Ecology and Environmental Sciences,2010,19(9):2232-2239(in Chinese)
[39]Van Aggelen G,Ankley G T,Baldwin W S,et al.Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring:Hurdles,achievements,and future outlook[J].Environmental Health Perspectives,2010,118(1):1-5
[40]Beaver L M,Truong L,Barton C L,et al.Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish(Danio rerio)development[J].PLoS One,2017,12(8):e0183831
[41]Haggard D E,Das S R,Tanguay R L.Comparative toxicogenomic responses to the flame retardant m ITP in developing zebrafish[J].Chemical Research in Toxicology,2017,30(2):508-515
[42]Wirbisky S E,Damayanti N P,Mahapatra C T,et al.Mitochondrial dysfunction,disruption of F-Actin polymerization,and transcriptomic alterations in zebrafish larvae exposed to trichloroethylene[J].Chemical Research in Toxicology,2016,29(2):169-179
[43]Li C,Chen Q,Zhang X,et al.An integrated approach with the zebrafish model for biomonitoring of municipal wastewater effluent and receiving waters[J].Water Research,2017,131:33-44
[44]张家敏,彭颖,方文迪,等.有害结局路径(AOP)框架在水体复合污染监测研究中的应用[J].生态毒理学报,2017,12(1):1-14Zhang J M,Peng Y,Fang W D,et al.Application of adverse outcome pathways framework in monitoring of toxic chemicals from aquatic environments[J].Asian Journal of Ecotoxicology,2017,12(1):1-14(in Chinese)
[45]Beausoleil C,Ormsby J N,Gies A,et al.Low dose effects and non-monotonic dose responses for endocrine active chemicals:Science to practice workshop:Workshop summary[J].Chemosphere,2013,93(6):847-856
[46]Faulk C,Kim J H,Jones T R,et al.Bisphenol A-associated alterations in genome-wide DNA methylation and gene expression patterns reveal sequence-dependent and non-monotonic effects in human fetal liver[J].Environmental Epigenetics,2015,1(1):dvv006
[47]Fetter E,Smetanova S,Baldauf L,et al.Identification and characterization of androgen-responsive genes in zebrafish embryos[J].Environmental Science&Technology,2015,49(19):11789-11798
[48]Berninger J P,Martinovi'c-Weigelt D,Garcia-Reyero N,et al.Using transcriptomic tools to evaluate biological effects across effluent gradients at a diverse set of study sites in Minnesota,USA[J].Environmental Science&Technology,2014,48(4):2404-2412
[49]Smetanova S,Riedl J,Zitzkat D,et al.High-throughput concentration-response analysis for omics datasets[J].Environmental Toxicology and Chemistry,2015,34(9):2167-2180
[50]Thomas R S,Allen B C,Nong A,et al.A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure[J].Toxicological Sciences,2007,98(1):240-248
[51]Bild A H,Yao G,Chang J T,et al.Oncogenic pathway signatures in human cancers as a guide to targeted therapies[J].Nature,2006,439(7074):353-357
[52]Xia P,Zhang X,Zhang H,et al.Benchmarking water quality from wastewater to drinking waters using reduced transcriptome of human cells[J].Environmental Science&Technology,2017,51(16):9318-9326
[53]Wang P,Xia P,Yang J,et al.A reduced transcriptome approach to assess environmental toxicants using zebrafish embryo test[J].Environmental Science&Technology,2018,52(2):821-830
[2]Judson R,Richard A,Dix D J,et al.The toxicity data landscape for environmental chemicals[J].Environmental Health Perspectives,2009,117(5):685-695
[3]刘辉,戴家银.斑马鱼在生态毒理学研究及环境监测中的应用[J].中国实验动物学报,2015,23(5):529-534Liu H,Dai J Y.Application of zebrafish(Danio rerio)in the fields of environmental ecotoxicology and environmental monitoring[J].Acta Laboratorium Animals Scientia Sinica,2015,23(5):529-534(in Chinese)
[4]Zhang X,Xia P,Wang P,et al.Omics advances in ecotoxicology[J].Environmental Science&Technology,2018,52(7):3842-3851
[5]Collins F S,Gray G M,Bucher J R.Transforming environmental health protection[J].Science,2008,319(5865):906-907
[6]Schwarzenbach R P,Escher B I,Fenner K,et al.The challenge of micropollutants in aquatic systems[J].Science,2006,313(5790):1072-1077
[7]Altenburger R,Ait-Aissa S,Antczak P,et al.Future water quality monitoring-Adapting tools to deal with mixtures of pollutants in water resource management[J].Science of The Total Environment,2015,512-513:540-551
[8]Kavlock R,Chandler K,Houck K,et al.Update on EPA's Tox Cast program:Providing high throughput decision support tools for chemical risk management[J].Chemical Research in Toxicology,2012,25(7):1287-1302
[9]Brack W,Schmitt-Jansen M,Machala M,et al.How to confirm identified toxicants in effect-directed analysis[J].Analytical and Bioanalytical Chemistry,2008,390(8):1959-1973
[10]Connon R E,Geist J,Werner I.Effect-based tools for monitoring and predicting the ecotoxicological effects of chemicals in the aquatic environment[J].Sensors,2012,12(9):12741-12771
[11]Li H,Zhang J,You J.Diagnosis of complex mixture toxicity in sediments:Application of toxicity identification evaluation(TIE)and effect-directed analysis(EDA)[J].Environmental Pollution,2017,237:944-954
[12]de Esch C,Slieker R,Wolterbeek A,et al.Zebrafish as potential model for developmental neurotoxicity testing:A mini review[J].Neurotoxicology and Teratology,2012,34(6):545-553
[13]Sipes N S,Padilla S,Knudsen T B.Zebrafish:As an integrative model for twenty-first century toxicity testing[J].Birth Defects Research Part C:Embryo Today:Reviews,2011,93(3):256-267
[14]Sobanska M,Scholz S,Nyman A M,et al.Applicability of the fish embryo acute toxicity(FET)test(OECD236)in the regulatory context of Registration,Evaluation,Authorisation,and Restriction of Chemicals(REACH)[J].Environmental Toxicology and Chemistry,2018,37(3):657-670
[15]Di Paolo C,Seiler T-B,Keiter S,et al.The value of zebrafish as an integrative model in effect-directed analysis-A review[J].Environmental Sciences Europe,2015,27(1):8-19
[16]McCollum C W,Ducharme N A,Bondesson M,et al.Developmental toxicity screening in zebrafish[J].Birth Defects Research Part C:Embryo Today:Reviews,2011,93(2):67-114
[17]Hallare A,Nagel K,Kohler H R,et al.Comparative embryotoxicity and proteotoxicity of three carrier solvents to zebrafish(Danio rerio)embryos[J].Ecotoxicology and Environmental Safety,2006,63(3):378-388
[18]Noyes P D,Garcia G R,Tanguay R L.Zebrafish as an in vivo model for sustainable chemical design[J].Green Chemistry,2016,18(24):6410-6430
[19]Mandrell D,Truong L,Jephson C,et al.Automated zebrafish chorion removal and single embryo placement:Optimizing throughput of zebrafish developmental toxicity screens[J].Journal of Laboratory Automation,2012,17(1):66-74
[20]Yozzo K L,Isales G M,Raftery T D,et al.High-content screening assay for identification of chemicals impacting cardiovascular function in zebrafish embryos[J].Environmental Science&Technology,2013,47(19):11302-11310
[21]Padilla S,Corum D,Padnos B,et al.Zebrafish developmental screening of the Tox Cast Phase I chemical library[J].Reprodutive Toxicology,2012,33(2):174-187
[22]Reif D M,Truong L,Mandrell D,et al.High-throughput characterization of chemical-associated embryonic behavioral changes predicts teratogenic outcomes[J].Archives of Toxicology,2016,90(6):1459-1470
[23]Truong L,Reif D M,St Mary L,et al.Multidimensional in vivo hazard assessment using zebrafish[J].Toxicological Sciences,2014,137(1):212-233
[24]Zhang G,Truong L,Tanguay R L,et al.A new statistical approach to characterize chemical-elicited behavioral effects in high-throughput studies using zebrafish[J].PLoS One,2017,12(1):e0169408
[25]Kokel D,Dunn T W,Ahrens M B,et al.Identification of nonvisual photomotor response cells in the vertebrate hindbrain[J].The Journal of Neuroscience,2013,33(9):3834-3843
[26]Tierney K B.Behavioural assessments of neurotoxic effects and neurodegeneration in zebrafish[J].Biochimica Biophysica Acta,2011,1812(3):381-389
[27]Bruni G,Rennekamp A J,Velenich A,et al.Zebrafish behavioral profiling identifies multitarget antipsychoticlike compounds[J].Nature Chemical Biology,2016,12(7):559-566
[28]Kokel D,Bryan J,Laggner C,et al.Rapid behavior-based identification of neuroactive small molecules in the zebrafish[J].Nature Chemical Biology,2010,6(3):231-237
[29]Noyes P D,Haggard D E,Gonnerman G D,et al.Advanced morphological-behavioral test platform reveals neurodevelopmental defects in embryonic zebrafish exposed to comprehensive suite of halogenated and organophosphate flame retardants[J].Toxicological Sciences,2015,145(1):177-195
[30]Kluver N,Konig M,Ortmann J,et al.Fish embryo toxicity test:Identification of compounds with weak toxicity and analysis of behavioral effects to improve prediction of acute toxicity for neurotoxic compounds[J].Environmental Science&Technology,2015,49(11):7002-7011
[31]Zhang K,Zhao Y,Fent K,et al.Occurrence and ecotoxicological effects of free,conjugated,and halogenated steroids including 17alpha-hydroxypregnanolone and pregnanediol in Swiss wastewater and surface water[J].Environmental Science&Technology,2017,51(11):6498-6506
[32]Chen M,Zhang M,Borlak J,et al.A decade of toxicogenomic research and its contribution to toxicological science[J].Toxicological Sciences,2012,130(2):217-228
[33]Simmons D B,Benskin J P,Cosgrove J R,et al.Omics for aquatic ecotoxicology:Control of extraneous variability to enhance the analysis of environmental effects[J].Environmental Toxicology and Chemistry,2015,34(8):1693-1704
[34]Yan S-K,Liu R-H,Jin H-Z,et al.“Omics”in pharmaceutical research:Overview,applications,challenges,and future perspectives[J].Chinese Journal of Natural Medicines,2015,13(1):3-21
[35]Antczak P,Jo H J,Woo S,et al.Molecular toxicity identification evaluation(m TIE)approach predicts chemical exposure in Daphnia magna[J].Environmental Science&Technology,2013,47(20):11747-11756
[36]Schaap M M,Wackers P F,Zwart E P,et al.A novel toxicogenomics-based approach to categorize(non-)genotoxic carcinogens[J].Archives of Toxicology,2015,89(12):2413-2427
[37]Peng Y,Xia P,Zhang J,et al.Toxicogenomic assessment of 6-OH-BDE47-induced developmental toxicity in chicken embryos[J].Environmental Science&Technology,2016,50(22):12493-12503
[38]陆韻,侯凌燕,胡洪营,等.毒理基因组学研究进展[J].生态环境学报,2010,19(9):2232-2239Lu X,Hou L Y,Hu H Y,et al.Progress in toxicogenomics[J].Ecology and Environmental Sciences,2010,19(9):2232-2239(in Chinese)
[39]Van Aggelen G,Ankley G T,Baldwin W S,et al.Integrating omic technologies into aquatic ecological risk assessment and environmental monitoring:Hurdles,achievements,and future outlook[J].Environmental Health Perspectives,2010,118(1):1-5
[40]Beaver L M,Truong L,Barton C L,et al.Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish(Danio rerio)development[J].PLoS One,2017,12(8):e0183831
[41]Haggard D E,Das S R,Tanguay R L.Comparative toxicogenomic responses to the flame retardant m ITP in developing zebrafish[J].Chemical Research in Toxicology,2017,30(2):508-515
[42]Wirbisky S E,Damayanti N P,Mahapatra C T,et al.Mitochondrial dysfunction,disruption of F-Actin polymerization,and transcriptomic alterations in zebrafish larvae exposed to trichloroethylene[J].Chemical Research in Toxicology,2016,29(2):169-179
[43]Li C,Chen Q,Zhang X,et al.An integrated approach with the zebrafish model for biomonitoring of municipal wastewater effluent and receiving waters[J].Water Research,2017,131:33-44
[44]张家敏,彭颖,方文迪,等.有害结局路径(AOP)框架在水体复合污染监测研究中的应用[J].生态毒理学报,2017,12(1):1-14Zhang J M,Peng Y,Fang W D,et al.Application of adverse outcome pathways framework in monitoring of toxic chemicals from aquatic environments[J].Asian Journal of Ecotoxicology,2017,12(1):1-14(in Chinese)
[45]Beausoleil C,Ormsby J N,Gies A,et al.Low dose effects and non-monotonic dose responses for endocrine active chemicals:Science to practice workshop:Workshop summary[J].Chemosphere,2013,93(6):847-856
[46]Faulk C,Kim J H,Jones T R,et al.Bisphenol A-associated alterations in genome-wide DNA methylation and gene expression patterns reveal sequence-dependent and non-monotonic effects in human fetal liver[J].Environmental Epigenetics,2015,1(1):dvv006
[47]Fetter E,Smetanova S,Baldauf L,et al.Identification and characterization of androgen-responsive genes in zebrafish embryos[J].Environmental Science&Technology,2015,49(19):11789-11798
[48]Berninger J P,Martinovi'c-Weigelt D,Garcia-Reyero N,et al.Using transcriptomic tools to evaluate biological effects across effluent gradients at a diverse set of study sites in Minnesota,USA[J].Environmental Science&Technology,2014,48(4):2404-2412
[49]Smetanova S,Riedl J,Zitzkat D,et al.High-throughput concentration-response analysis for omics datasets[J].Environmental Toxicology and Chemistry,2015,34(9):2167-2180
[50]Thomas R S,Allen B C,Nong A,et al.A method to integrate benchmark dose estimates with genomic data to assess the functional effects of chemical exposure[J].Toxicological Sciences,2007,98(1):240-248
[51]Bild A H,Yao G,Chang J T,et al.Oncogenic pathway signatures in human cancers as a guide to targeted therapies[J].Nature,2006,439(7074):353-357
[52]Xia P,Zhang X,Zhang H,et al.Benchmarking water quality from wastewater to drinking waters using reduced transcriptome of human cells[J].Environmental Science&Technology,2017,51(16):9318-9326
[53]Wang P,Xia P,Yang J,et al.A reduced transcriptome approach to assess environmental toxicants using zebrafish embryo test[J].Environmental Science&Technology,2018,52(2):821-830
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |