Transgenic Animal Models in Toxicology: Historical Perspectives and Future Outlook

Toxicology and Environmental Research and Consulting, The Dow Chemical Company, Midland, Michigan 48674, USA.
Toxicological Sciences (Impact Factor: 4.48). 03/2011; 121(2):207-33. DOI: 10.1093/toxsci/kfr075
Source: PubMed

ABSTRACT 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.

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    • "In addition to these in vivo models, transgenic animals are also increasingly being used to understand the mechanisms of biological processes (diseases) and toxicological endpoints (carcinogenicity and mutagenicity) (Boverhof et al., 2011; Gonzalez et al., 1998); however, these transgenic models are not developed specifically to study inhibition of apoptosis in hepatocarcinogenesis, thus is beyond the scope of this review. Some of the limitations of in vivo models are as follows: (1) rate of apoptosis: in the normal rodent liver rate of apoptosis varies from 0.01 to 0.05% (Chopra et al., 2009). "
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