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Toxicologic Pathology, Vol. 28, No. 3,
482-499 (2000)
DOI: 10.1177/019262330002800320
Review Article: Use of Transgenic Animals for Carcinogenicity Testing: Considerations and Implications for Risk Assessment
Donna Gulezian
Taconic Farms, Inc, Madison, Connecticut 06443
David Jacobson-Kram
BioReliance, Rockville, Maryland 20850
C. Bruce Mccullough
Aventis Pharmaceutical Products, Collegeville, Pennsylvania 19426
Harry Olson
Pfizer Central Research, Groton, Connecticut 06340
Leslie Recio
Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina 27709
Denise Robinson
ILSI Health and Environmental Sciences Institute, Washington, DC 20036
Richard Storer
Merck Research Laboratories, West Point, Pennsylvania 27709
Raymond Tennant
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709
Jerrold M. Ward
National Cancer Institute, Frederick, Maryland 21702
David A. Neumann
ILSI Risk Science Institute, Washington, DC 20036, dneumann{at}ilsi.org
Advances in genetic engineering have created opportunities for improved understanding of the molecular basis of carcinogenesis. Through selective introduction, activation, and inactivation of specific genes, investigators can produce mice of unique genotypes and phenotypes that afford insights into the events and mechanisms responsible for tumor formation. It has been suggested that such animals might be used for routine testing of chemicals to determine their carcinogenic potential because the animals may be mechanistically relevant for understanding and predicting the human response to exposure to the chemical being tested. Before transgenic and knockout mice can be used as an adjunct or alternative to the conventional 2-year rodent bioassay, information related to the animal line to be used, study design, and data analysis and interpretation must be carefully considered. Here, we identify and review such information relative to Tg.AC and rasH2 transgenic mice and p53+/- and XPA -/- knockout mice, all of which have been proposed for use in chemical carcinogenicity testing. In addition, the implications of findings of tumors in transgenic and knockout animals when exposed to chemicals is discussed in the context of human health risk assessment.
Key Words: Transgenic animals • knockout animals • carcinogenicity testing • risk assessment • carcinogens • bioassay
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