The p53 heterozygous knockout mouse as a model for chemical carcinogenesis in vascular tissue.
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.
Carmichael
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Rhône-Poulenc Agro, Centre de Recherche, Sophia Antipolis, France. neil.carmichael@sophia.rhone-poulenc.com
Debruyne
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Bigot-Lasserre
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D000818:Animals; D002273:Carcinogens / Q000009:adverse effects / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D016158:Genes, p53 / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D014520:Urethane / Q000009:adverse effects / Q000494:pharmacology; D019043:Vascular Neoplasms / Q000139:chemically induced* / Q000209:etiology / Q000235:genetics
D002273:Carcinogens; D014520:Urethane