| The p53 Heterozygous Knockout Mouse as a Model for Chemical Carcinogenesis in Vascular Tissue Neil G. Carmichael, Eric L.M. Debruyne, and Dominique Bigot-Lasserre Rhône-Poulenc Agro, Centre de Recherche, Sophia Antipolis, France Abstract
Heterozygous p53 knockout mice were investigated as a potential model for vascular tumor carcinogenesis. Groups of 20 male mice were exposed by gavage for 6 months to the vascular carcinogen urethane at 1, 10, or 100 mg/kg body weight/day. Wild-type and heterozygous p53 knockout control groups were exposed by gavage to the vehicle alone. Another group of 20 male mice received d-limonene by gavage (d-limonene is noncarcinogenic in mice) . The high dose of urethane caused early mortality in the majority of mice associated with histopathologic evidence of toxicity and tumors, including a high incidence of benign and malignant vascular tumors, in all animals. At the intermediate dose, toxicity was less marked and 3 of 20 mice had tumors ; mice that received the low dose did not have signs of toxicity or neoplasia. The two control groups had no tumors and the d-limonene group had one tumor of the prostate, which was considered spontaneous. We conclude that the p53 knockout mouse is a useful tool for investigating vascular tumorogenesis. Key words: carcinogenicity models, p53 knockout mouse, vascular tumors. Environ Health Perspect 108:61-65 (2000) . [Online 14 December 1999] http://ehpnet1.niehs.nih.gov/docs/2000/108p61-65carmichael/ abstract.html Address correspondence to N.G. Carmichael, Rhône-Poulenc Agro, Centre de Recherche, 355 rue Dostoievski, B.P. 153, F-06903 Sophia Antipolis Cedex, France. Telephone: 33 4 92 94 34 02. Fax: 33 4 93 65 41 39. E-mail: neil.carmichael@sophia.rhone-poulenc.com Received 11 February 1999 ; accepted 19 August 1999. Address correspondence to N.G. Carmichael, Rhône-Poulenc Agro, Centre de Recherche, 355 rue Dostoievski, B.P. 153, F-06903 Sophia Antipolis Cedex, France. Telephone: 33 4 92 94 34 02. Fax: 33 4 93 65 41 39. E-mail: neil.carmichael@sophia.rhone-poulenc.com Received 11 February 1999 ; accepted 19 August 1999.
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