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田明明, 夏普, 张效伟. 功能基因组学在环境化学品毒性机制研究中的应用[J]. 生态毒理学报, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
引用本文: 田明明, 夏普, 张效伟. 功能基因组学在环境化学品毒性机制研究中的应用[J]. 生态毒理学报, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
shu
Tian Mingming, Xia Pu, Zhang Xiaowei. Applications of Functional Genomics in Uncovering the Toxicity Mechanisms of Environmental Chemicals[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
Citation: Tian Mingming, Xia Pu, Zhang Xiaowei. Applications of Functional Genomics in Uncovering the Toxicity Mechanisms of Environmental Chemicals[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
shu

功能基因组学在环境化学品毒性机制研究中的应用

  • 1. 污染控制与资源化研究国家重点实验室, 南京大学环境学院, 南京 210023;

  • 2. 江苏省生态环境保护化学品安全与健康风险研究重点实验室, 南京 210023

    • 作者简介: 田明明(1994-),男,博士研究生,研究方向为环境功能基因组学,E-mail:tianzhuangm@126.com
    通讯作者: 张效伟, E-mail: zhangxw@nju.edu.cn
  • 基金项目:

    国家重点研发计划课题(2019YFC1804004)

    国家自然科学基金资助项目(41977206)

    江苏环境保护研究基金资助项目(2018001)

  • 中图分类号: X171.5

Applications of Functional Genomics in Uncovering the Toxicity Mechanisms of Environmental Chemicals

  • 1. State Key Laboratory of Pollution Control & Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China;

  • 2. Jiangsu Province Ecology and Environment Protection Key Laboratory of Chemical Safety and Health Risk, Nanjing 210023, China

    • Corresponding author: Zhang Xiaowei, zhangxw@nju.edu.cn
  • Fund Project:

  • 摘要: 认识化学品的毒性机制是开展化学品健康风险评估的基础。掌握化学品有害效应的遗传易感性机制是开展精准的健康风险评估的前提。传统的毒理基因组学主要分析化学品暴露诱导的组学表达图谱，不能建立生物学表型与特定基因/通路表达的直接关联。功能基因组学通过敲除或者敲降全基因组或者特定的基因集，建立基因-化学品毒性的直接关联，进而研究化学品致毒的过程和机制，同时可以提供与化学品暴露的遗传易感性相关的分子响应信息。本论文综述了功能基因组学技术的原理及其主要发展，介绍了酵母、鸡DT40细胞和RNA干扰等功能基因组学测试方法的优缺点。同时，详述了CRISPR功能基因组学的原理和特点，以及其在化学品毒性机制研究中的应用，展望了联合应用分子流行病学和CRISPR功能基因组学，开展化学品有害效应的易感性机制研究。
    Abstract: Understanding the biological mechanisms of toxic effects is essential for human health risk assessments of environmental chemicals. Significant uncertainties in risk assessment were caused by the different susceptibility of human individuals due to genetic variation. Knowledge of the molecular mechanisms underlying the genetic susceptibility to adverse effects of environmental chemicals could enhance the assessment of health risk. Conventional toxicogenomics approaches, such as transcriptomics, have been proved to facilitate the discovery of potential toxicological mechanisms of environmental chemicals by measuring the differentially expressed genes. However, these approaches failed to identify the direct connections between expressions of genes/pathways and toxicological phenotypes. Functional genomics screens could identify the direct links between specific genes and adverse effects of environmental chemicals by systematic knockout or knockdown of genes or gene sets in a genome-scale. Therefore, functional genomics screens can reveal the mechanisms of action of toxic chemicals and uncover key genes which are involved in the variated susceptibility to chemicals exposure. This review presented the recent advances in functional toxicogenomic of environmental chemicals, and the strength and limitations of some conventional functional genomics, including yeast, chicken DT40 cells, haploid mammalian cells and RNA interference. Furthermore, this review clarified the mechanisms and characteristics of CRISPR-Cas9 functional genomic screen of environmental chemicals. Finally, it is prospected that the biological mechanisms underlying the genetic susceptibility to adverse effects of environmental chemicals could be uncovered by combined using of CRISPR screen and molecular epidemiology analysis.
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  • United Nations Environment Programme (UNEP). Global chemicals outlook:Towards sound management of chemicals[R]. Nairobi, Kenya:UNEP, 2013
    Rappaport S M, Smith M T. Environment and disease risks[J]. Science, 2010, 330(6003):460-461
    Gruber K. Cleaning up pollutants to protect future health[J]. Nature, 2018, 555(7695):S20-S22
    Cicero C E, Mostile G, Vasta R, et al. Metals and neurodegenerative diseases. A systematic review[J]. Environmental Research, 2017, 159:82-94
    Backhaus T, Faust M. Predictive environmental risk assessment of chemical mixtures:A conceptual framework[J]. Environmental Science&Technology, 2012, 46(5):2564-2573
    Syberg K, Hansen S F. Environmental risk assessment of chemicals and nanomaterials:The best foundation for regulatory decision-making?[J]. Science of the Total Environment, 2016, 541:784-794
    Farmahin R, Williams A, Kuo B, et al. Recommended approaches in the application of toxicogenomics to derive points of departure for chemical risk assessment[J]. Archives of Toxicology, 2017, 91(5):2045-2065
    Moffat I, Chepelev N, Labib S, et al. Comparison of toxicogenomics and traditional approaches to inform mode of action and points of departure in human health risk assessment of benzo[a]pyrene in drinking water[J]. Critical Reviews in Toxicology, 2015, 45(1):1-43
    Waters M D, Fostel J M. Toxicogenomics and systems toxicology:Aims and prospects[J]. Nature Reviews Genetics, 2004, 5(12):936-948
    Aardema M J, MacGregor J T. Toxicology and genetic toxicology in the new era of "toxicogenomics":Impact of "-omics" technologies[J]. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 2002, 499(1):13-25
    Zhang X W, Xia P, Wang P P, et al. Omics advances in ecotoxicology[J]. Environmental Science&Technology, 2018, 52(7):3842-3851
    Xia P, Zhang X W, Xie Y W, et al. Functional toxicogenomic assessment of triclosan in human HepG2 cells using genome-wide CRISPR-Cas9 screening[J]. Environmental Science&Technology, 2016, 50(19):10682-10692
    Lujan H, Romer E, Salisbury R, et al. Determining the biological mechanisms of action for environmental exposures:Applying CRISPR/Cas9 to toxicological assessments[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2020, 175(1):5-18
    de Jong K, Vonk J M, Imboden M, et al. Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure[J]. Respiratory Research, 2017, 18(1):142
    Smith B M, Traboulsi H, Austin J H M, et al. Human airway branch variation and chronic obstructive pulmonary disease[J]. Proceedings of the National Academy of Sciences of the United States of America, 2018, 115(5):E974-E981
    Khreis H, Kelly C, Tate J, et al. Exposure to traffic-related air pollution and risk of development of childhood asthma:A systematic review and meta-analysis[J]. Environment International, 2017, 100:1-31
    Thomas D. Gene:Environment-wide association studies:Emerging approaches[J]. Nature Reviews Genetics, 2010, 11(4):259-272
    Sepand M R, Aliomrani M, Hasani-Nourian Y, et al. Mechanisms and pathogenesis underlying environmental chemical-induced necroptosis[J]. Environmental Science and Pollution Research International, 2020, 27(30):37488-37501
    Rodgers K M, Udesky J O, Rudel R A, et al. Environmental chemicals and breast cancer:An updated review of epidemiological literature informed by biological mechanisms[J]. Environmental Research, 2018, 160:152-182
    Shen H, McHale C M, Smith M T, et al. Functional genomic screening approaches in mechanistic toxicology and potential future applications of CRISPR-Cas9[J]. Mutation Research Reviews in Mutation Research, 2015, 764:31-42
    Jo W J, Loguinov A, Wintz H, et al. Comparative functional genomic analysis identifies distinct and overlapping sets of genes required for resistance to monomethylarsonous acid (MMAⅢ) and arsenite (AsⅢ) in yeast[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2009, 111(2):424-436
    Zhou Y X, Zhu S Y, Cai C Z, et al. High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells[J]. Nature, 2014, 509(7501):487-491
    Shortt K, Heruth D P, Zhang N N, et al. Identification of novel regulatory genes in APAP induced hepatocyte toxicity by a genome-wide CRISPR-Cas9 screen[J]. Scientific Reports, 2019, 9(1):1396
    Guan M, Xia P, Tian M M, et al. Molecular fingerprints of conazoles via functional genomic profiling of Saccharomyces cerevisiae [J]. Toxicology in Vitro:An International Journal Published in Association with BIBRA, 2020, 69:104998
    Chow R D, Chen S D. Cancer CRISPR screens in vivo [J]. Trends in Cancer, 2018, 4(5):349-358
    Shan G. RNA interference as a gene knockdown technique[J]. The International Journal of Biochemistry&Cell Biology, 2010, 42(8):1243-1251
    Zhang F, Wen Y, Guo X. CRISPR/Cas9 for genome editing:Progress, implications and challenges[J]. Human Molecular Genetics, 2014, 23(R1):R40-R46
    Shalem O, Sanjana N E, Hartenian E, et al. Genome-scale CRISPR-Cas9 knockout screening in human cells[J]. Science, 2014, 343(6166):84-87
    Cenik C, Cenik E S, Byeon G W, et al. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans[J]. Genome Research, 2015, 25(11):1610-1621
    Reczek C R, Birsoy K, Kong H, et al. A CRISPR screen identifies a pathway required for paraquat-induced cell death[J]. Nature Chemical Biology, 2017, 13(12):1274-1279
    Bassett D E, Boguski M S, Hieter P. Yeast genes and human disease[J]. Nature, 1996, 379(6566):589-590
    Scherens B, Goffeau A. The uses of genome-wide yeast mutant collections[J]. Genome Biology, 2004, 5(7):229
    Steinmetz L M, Scharfe C, Deutschbauer A M, et al. Systematic screen for human disease genes in yeast[J]. Nature Genetics, 2002, 31(4):400-404
    Yamazoe M, Sonoda E, Hochegger H, et al. Reverse genetic studies of the DNA damage response in the chicken B lymphocyte line DT40[J]. DNA Repair, 2004, 3(8-9):1175-1185
    Ji K, Kogame T, Choi K, et al. A novel approach using DNA-repair-deficient chicken DT40 cell lines for screening and characterizing the genotoxicity of environmental contaminants[J]. Environmental Health Perspectives, 2009, 117(11):1737-1744
    Ooka M, Takazawa H, Takeda S, et al. Cytotoxic and genotoxic profiles of benzo[a]pyrene and N-nitrosodimethylamine demonstrated using DNA repair deficient DT40 cells with metabolic activation[J]. Chemosphere, 2016, 144:1901-1907
    Kotecki M, Reddy P S, Cochran B H. Isolation and characterization of a near-haploid human cell line[J]. Experimental Cell Research, 1999, 252(2):273-280
    Pettitt S J, Rehman F L, Bajrami I, et al. A genetic screen using the PiggyBac transposon in haploid cells identifies Parp1 as a mediator of olaparib toxicity[J]. PLoS One, 2013, 8(4):e61520
    Duncan L M, Timms R T, Zavodszky E, et al. Fluorescence-based phenotypic selection allows forward genetic screens in haploid human cells[J]. PLoS One, 2012, 7(6):e39651
    Leeb M, Wutz A. Derivation of haploid embryonic stem cells from mouse embryos[J]. Nature, 2011, 479(7371):131-134
    Wolters N M, MacKeigan J P. From sequence to function:Using RNAi to elucidate mechanisms of human disease[J]. Cell Death&Differentiation, 2008, 15(5):809-819
    Root D E, Hacohen N, Hahn W C, et al. Genome-scale loss-of-function screening with a lentiviral RNAi library[J]. Nature Methods, 2006, 3(9):715-719
    Mohr S E, Smith J A, Shamu C E, et al. RNAi screening comes of age:Improved techniques and complementary approaches[J]. Nature Reviews Molecular Cell Biology, 2014, 15(9):591-600
    Zheng Q P, Cai X H, Tan M H, et al. Precise gene deletion and replacement using the CRISPR/Cas9 system in human cells[J]. BioTechniques, 2014, 57(3):115-124
    Costanzo M C, Hogan J D, Cusick M E, et al. The yeast proteome database (YPD) and Caenorhabditis elegans proteome database (WormPD):Comprehensive resources for the organization and comparison of model organism protein information[J]. Nucleic Acids Research, 2000, 28(1):73-76
    Parsons A B, Geyer R, Hughes T R, et al. Yeast genomics and proteomics in drug discovery and target validation[J]. Progress in Cell Cycle Research, 2003, 5:159-166
    O'Connor S T, Lan J Q, North M, et al. Genome-wide functional and stress response profiling reveals toxic mechanism and genes required for tolerance to benzo[a]pyrene in S. cerevisiae [J]. Frontiers in Genetics, 2012, 3:316
    de Graaf B, Clore A, McCullough A K. Cellular pathways for DNA repair and damage tolerance of formaldehyde-induced DNA-protein crosslinks[J]. DNA Repair, 2009, 8(10):1207-1214
    Ren X F, Lim S, Ji Z Y, et al. Comparison of proliferation and genomic instability responses to WRN silencing in hematopoietic HL60 and TK6 cells[J]. PLoS One, 2011, 6(1):e14546
    Ren X F, Aleshin M, Jo W J, et al. Involvement of N-6 adenine-specific DNA methyltransferase 1(N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity[J]. Environmental Health Perspectives, 2011, 119(6):771-777
    Buerstedde J M, Takeda S. Increased ratio of targeted to random integration after transfection of chicken B cell lines[J]. Cell, 1991, 67(1):179-188
    Evans T J, Yamamoto K N, Hirota K, et al. Mutant cells defective in DNA repair pathways provide a sensitive high-throughput assay for genotoxicity[J]. DNA Repair, 2010, 9(12):1292-1298
    Mizutani A, Okada T, Shibutani S, et al. Extensive chromosomal breaks are induced by tamoxifen and estrogen in DNA repair-deficient cells[J]. Cancer Research, 2004, 64(9):3144-3147
    Ji K, Choi K, Giesy J P, et al. Genotoxicity of several polybrominated diphenyl ethers (PBDEs) and hydroxylated PBDEs, and their mechanisms of toxicity[J]. Environmental Science&Technology, 2011, 45(11):5003-5008
    Andersson B S, Beran M, Pathak S, et al. pH-positive chronic myeloid leukemia with near-haploid conversion in vivo and establishment of a continuously growing cell line with similar cytogenetic pattern[J]. Cancer Genetics and Cytogenetics, 1987, 24(2):335-343
    Carette J E, Raaben M, Wong A C, et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1[J]. Nature, 2011, 477(7364):340-343
    Birsoy K, Wang T, Possemato R, et al. MCT1-mediated transport of a toxic molecule is an effective strategy for targeting glycolytic tumors[J]. Nature Genetics, 2013, 45(1):104-108
    Shen H, McHale C M, Haider S I, et al. Identification of genes that modulate susceptibility to formaldehyde and imatinib by functional genomic screening in human haploid KBM7 cells[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2016, 154(1):194
    Lee C C, Carette J E, Brummelkamp T R, et al. A reporter screen in a human haploid cell line identifies CYLD as a constitutive inhibitor of NF-κ B[J]. PLoS One, 2013, 8(7):e70339
    Elling U, Taubenschmid J, Wirnsberger G, et al. Forward and reverse genetics through derivation of haploid mouse embryonic stem cells[J]. Cell Stem Cell, 2011, 9(6):563-574
    Li W, Shuai L, Wan H F, et al. Androgenetic haploid embryonic stem cells produce live transgenic mice[J]. Nature, 2012, 490(7420):407-411
    Carette J E, Pruszak J, Varadarajan M, et al. Generation of iPSCs from cultured human malignant cells[J]. Blood, 2010, 115(20):4039-4042
    Rana T M. Illuminating the silence:Understanding the structure and function of small RNAs[J]. Nature Reviews Molecular Cell Biology, 2007, 8(1):23-36
    Willingham A T, Deveraux Q L, Hampton G M, et al. RNAi and HTS:Exploring cancer by systematic loss-of-function[J]. Oncogene, 2004, 23(51):8392-8400
    Fennell M, Xiang Q, Hwang A, et al. Impact of RNA-guided technologies for target identification and deconvolution[J]. Journal of Biomolecular Screening, 2014, 19(10):1327-1337
    Park H R, Oh R, Wagner P, et al. New Insights into Cellular Stress Responses to Environmental Metal Toxicants[M]//Galluzzi L. Ed. International Review of Cell and Molecular Biology. Elsevier B.V., 2017, 331:55-82
    Oh R S, Pan W C, Yalcin A, et al. Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2(SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress[J]. The Journal of Biological Chemistry, 2012, 287(8):6025-6034
    Berns K, Bernards R. Understanding resistance to targeted cancer drugs through loss of function genetic screens[J]. Drug Resistance Updates, 2012, 15(5-6):268-275
    Swanton C, Marani M, Pardo O, et al. Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs[J]. Cancer Cell, 2007, 11(6):498-512
    Singel S M, Cornelius C, Batten K, et al. A targeted RNAi screen of the breast cancer genome identifies KIF14 and TLN1 as genes that modulate docetaxel chemosensitivity in triple-negative breast cancer[J]. Clinical Cancer Research:An Official Journal of the American Association for Cancer Research, 2013, 19(8):2061-2070
    Schmidt E E, Pelz O, Buhlmann S, et al. GenomeRNAi:A database for cell-based and in vivo RNAi phenotypes, 2013 update[J]. Nucleic Acids Research, 2013, 41(Database issue):D1021-D1026
    Ngo V N, Davis R E, Lamy L, et al. A loss-of-function RNA interference screen for molecular targets in cancer[J]. Nature, 2006, 441(7089):106-110
    Bassik M C, Lebbink R J, Churchman L S, et al. Rapid creation and quantitative monitoring of high coverage shRNA libraries[J]. Nature Methods, 2009, 6(6):443-445
    Cong L, Ran F A, Cox D, et al. Multiplex genome engineering using CRISPR/Cas systems[J]. Science, 2013, 339(6121):819-823
    Jinek M, East A, Cheng A, et al. RNA-programmed genome editing in human cells[J]. eLife, 2013, 2:e00471
    Blanchard A P, Hood L. Sequence to array:Probing the genome's secrets[J]. Nature Biotechnology, 1996, 14(13):1649
    Sander J D, Joung J K. CRISPR-Cas systems for editing, regulating and targeting genomes[J]. Nature Biotechnology, 2014, 32(4):347-355
    Wang T, Wei J J, Sabatini D M, et al. Genetic screens in human cells using the CRISPR-Cas9 system[J]. Science, 2014, 343(6166):80-84
    Sanjana N E, Shalem O, Zhang F. Improved vectors and genome-wide libraries for CRISPR screening[J]. Nature Methods, 2014, 11(8):783-784
    Koike-Yusa H, Li Y L, Tan E P, et al. Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library[J]. Nature Biotechnology, 2014, 32(3):267-273
    Joung J, Konermann S, Gootenberg J S, et al. Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening[J]. Nature Protocols, 2017, 12(4):828-863
    Bredesen D E, Rao R V, Mehlen P. Cell death in the nervous system[J]. Nature, 2006, 443(7113):796-802
    Baltazar M T, Dinis-Oliveira R J, de Lourdes Bastos M, et al. Pesticides exposure as etiological factors of Parkinson's Disease and other neurodegenerative diseases:A mechanistic approach[J]. Toxicology Letters, 2014, 230(2):85-103
    Dinwiddie M T, Terry P D, Chen J G. Recent evidence regarding triclosan and cancer risk[J]. International Journal of Environmental Research and Public Health, 2014, 11(2):2209-2217
    Kalloo G, Calafat A M, Chen A M, et al. Early life triclosan exposure and child adiposity at 8 Years of age:A prospective cohort study[J]. Environmental Health:A Global Access Science Source, 2018, 17(1):24
    Sobh A, Loguinov A, Stornetta A, et al. Genome-wide CRISPR screening identifies the tumor suppressor candidate OVCA2 as a determinant of tolerance to acetaldehyde[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2019, 169(1):235-245
    Sobh A, Loguinov A, Yazici G N, et al. Functional profiling identifies determinants of arsenic trioxide cellular toxicity[J]. Toxicological Sciences:An Official Journal of the Society of Toxicology, 2019, 169(1):108-121
    Panganiban R A, Park H R, Sun M Y, et al. Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2019, 116(27):13384-13393
    Liao Y J, Hao Y M, Chen H, et al. Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death[J]. Protein&Cell, 2015, 6(6):434-442
    Gogvadze V, Orrenius S, Zhivotovsky B. Analysis of mitochondrial dysfunction during cell death[J]. Methods in Molecular Biology, 2015, 1264:385-393
    Braun R J. Mitochondrion-mediated cell death:Dissecting yeast apoptosis for a better understanding of neurodegeneration[J]. Frontiers in Oncology, 2012, 2:182
    Tangamornsuksan W, Lohitnavy O, Sruamsiri R, et al. Paraquat exposure and Parkinson's Disease:A systematic review and meta-analysis[J]. Archives of Environmental&Occupational Health, 2019, 74(5):225-238
    Orth M. Mitochondrial involvement in Parkinson's Disease[J]. Neurochemistry International, 2002, 40(6):533-541
    Coelho M A, de Braekeleer E, Firth M, et al. CRISPR GUARD protects off-target sites from Cas9 nuclease activity using short guide RNAs[J]. Nature Communications, 2020, 11(1):4132
    Concordet J P, Haeussler M. CRISPOR:Intuitive guide selection for CRISPR/Cas9 genome editing experiments and screens[J]. Nucleic Acids Research, 2018, 46(W1):W242-W245
    Liu M S, Gong S Z, Yu H H, et al. Engineered CRISPR/Cas9 enzymes improve discrimination by slowing DNA cleavage to allow release of off-target DNA[J]. Nature Communications, 2020, 11(1):3576
    Liu Y, Chang J S, Yang C F, et al. Genome-wide CRISPR-Cas9 screening in Bombyx mori reveals the toxicological mechanisms of environmental pollutants, fluoride and cadmium[J]. Journal of Hazardous Materials, 2021, 410:124666
    Chen Y C, Tsai Y H, Wang C C, et al. Epigenome-wide association study on asthma and chronic obstructive pulmonary disease overlap reveals aberrant DNA methylations related to clinical phenotypes[J]. Scientific Reports, 2021, 11:5022
    Ren X W, Wen W, Fan X Y, et al. COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas[J]. Cell, 2021, 184(23):5838
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  • 收稿日期:  2021-10-01
田明明, 夏普, 张效伟. 功能基因组学在环境化学品毒性机制研究中的应用[J]. 生态毒理学报, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
引用本文: 田明明, 夏普, 张效伟. 功能基因组学在环境化学品毒性机制研究中的应用[J]. 生态毒理学报, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
shu
Tian Mingming, Xia Pu, Zhang Xiaowei. Applications of Functional Genomics in Uncovering the Toxicity Mechanisms of Environmental Chemicals[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
Citation: Tian Mingming, Xia Pu, Zhang Xiaowei. Applications of Functional Genomics in Uncovering the Toxicity Mechanisms of Environmental Chemicals[J]. Asian Journal of Ecotoxicology, 2022, 17(1): 1-17. doi: 10.7524/AJE.1673-5897.20211001001
shu

功能基因组学在环境化学品毒性机制研究中的应用

    通讯作者: 张效伟, E-mail: zhangxw@nju.edu.cn
    作者简介: 田明明(1994-),男,博士研究生,研究方向为环境功能基因组学,E-mail:tianzhuangm@126.com
  • 1. 污染控制与资源化研究国家重点实验室, 南京大学环境学院, 南京 210023;
  • 2. 江苏省生态环境保护化学品安全与健康风险研究重点实验室, 南京 210023
  • 收稿日期:  2021-10-01
基金项目:

国家重点研发计划课题(2019YFC1804004)

国家自然科学基金资助项目(41977206)

江苏环境保护研究基金资助项目(2018001)

摘要: 认识化学品的毒性机制是开展化学品健康风险评估的基础。掌握化学品有害效应的遗传易感性机制是开展精准的健康风险评估的前提。传统的毒理基因组学主要分析化学品暴露诱导的组学表达图谱，不能建立生物学表型与特定基因/通路表达的直接关联。功能基因组学通过敲除或者敲降全基因组或者特定的基因集，建立基因-化学品毒性的直接关联，进而研究化学品致毒的过程和机制，同时可以提供与化学品暴露的遗传易感性相关的分子响应信息。本论文综述了功能基因组学技术的原理及其主要发展，介绍了酵母、鸡DT40细胞和RNA干扰等功能基因组学测试方法的优缺点。同时，详述了CRISPR功能基因组学的原理和特点，以及其在化学品毒性机制研究中的应用，展望了联合应用分子流行病学和CRISPR功能基因组学，开展化学品有害效应的易感性机制研究。

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