The p53 heterozygous knockout mouse as a model for chemical carcinogenesisin vascular tissue

Heterozygous p53 knockout mice were investigated as a potential model for v ascular 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 bo dy weight/day. Wild-type and heterozygous p53 knockout control groups were exposed by gavage to the vehicle alone. Another group of 20 male mice recei ved A-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 inci dence of benign and malignant vascular tumors, in all animals. At the inter mediate dose, toxicity was less marked and 3 of 20 mice had tumors; mice th at received the low dose did not have signs of toxicity or neoplasia. The t wo control groups had no tumors and the d-limonene group had one tumor of t he prostate, which,vas considered spontaneous. We conclude that the p53 kno ckout mouse is a useful tool for investigating vascular tumorogenesis.