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Toxicologic Pathology
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The Tg.AC (v-Ha-ras) Transgenic Mouse: Nature of the Model

Raymond W. Tennant

National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709, tennant{at}niehs.nih.gov

Stanley Stasiewicz

National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709

William C. Eastin

National Institute of Environmental Health Sciences, Environmental Toxicology Program, Research Triangle Park, North Carolina 27709

John H. Mennear

103 Eagle Court, P.O. Box 5032, Cary, North Carolina 27511

Judson W. Spalding

National Institute of Environmental Health Sciences, Laboratory of Environmental Carcinogenesis and Mutagenesis, Research Triangle Park, North Carolina 27709

The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens. In common with the conventional bioassay, the Tg.AC model responds to known human carcinogens and does not respond to noncarcinogens. It also does not respond to most chemicals that are positive in conventional bioassays principally at sites of high spontaneous tumor incidence. The mechanism of response of the Tg.AC model is related to the structure and genomic position of the transgene and the induction of transgene expression through specific mediated interactions between the chemicals and target cells in the skin.

Key Words: Chemical carcinogens • alternative carcinogen bioassay • ras gene • transgenic mouse.

Toxicologic Pathology, Vol. 29, No. 1 suppl, 51-59 (2001)
DOI: 10.1080/019262301753178474


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