Transgenic Animal Models in Toxicology: Historical Perspectives and Future Outlook

被引:57
作者
Boverhof, Darrell R. [1 ]
Chamberlain, Mark P. [2 ]
Elcombe, Clifford R. [2 ]
Gonzalez, Frank J. [3 ]
Heflich, Robert H. [4 ]
Hernandez, Lya G. [5 ]
Jacobs, Abigail C. [6 ]
Jacobson-Kram, David [6 ]
Luijten, Mirjam [5 ]
Maggi, Adriana [6 ,7 ,8 ]
Manjanatha, Mugimane G. [4 ]
van Benthem, Jan [5 ]
Gollapudi, B. Bhaskar [1 ]
机构
[1] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA
[2] CXR Biosci Ltd, Dundee DD1 5JJ, Scotland
[3] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA
[4] US FDA, Natl Ctr Toxicol Research, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA
[5] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands
[6] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20933 USA
[7] Univ Milan, Dept Pharmacol Sci 3, Milan, Italy
[8] Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy
基金
美国国家卫生研究院;
关键词
transgenic models; knock-out models; humanized models; risk assessment; PREGNANE-X-RECEPTOR; ARYL-HYDROCARBON RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CYP1B1 DETERMINES SUSCEPTIBILITY; IN-VIVO; NUCLEAR RECEPTOR; TARGETED DISRUPTION; SPECIES-DIFFERENCES; DRUG-METABOLISM; HUMANIZED MOUSE;
D O I
10.1093/toxsci/kfr075
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Transgenic animal models are powerful tools for developing a more detailed understanding on the roles of specific genes in biological pathways and systems. Applications of these models have been made within the field of toxicology, most notably for the screening of mutagenic and carcinogenic potential and for the characterization of toxic mechanisms of action. It has long been a goal of research toxicologists to use the data from these models to refine hazard identification and characterization to better inform human health risk assessments. This review provides an overview on the applications of transgenic animal models in the assessment of mutagenicity and carcinogenicity, their use as reporter systems, and as tools for understanding the roles of xenobiotic-metabolizing enzymes and biological receptors in the etiology of chemical toxicity. Perspectives are also shared on the future outlook for these models in toxicology and risk assessment and how transgenic technologies are likely to be an integral tool for toxicity testing in the 21st century.
引用
收藏
页码:207 / 233
页数:27
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