Heterozygous p53-deficient mice are not susceptible to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) carcinogenicity

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a very potent muta gen which induces tumors in the liver, lung and hematopoietic system of CDF 1 mice and the liver, Zymbal gland and skin in F344 rats. The recent develo pment of transgenic knockout mice allows their introduction for sensitive s creening of environmental carcinogens due to the rapid development of tumor s. P53 gene deficient mice (p53-/-) were found to spontaneously develop mal ignant lymphoma and hemangiosarcoma, whereas heterozygotes (p53+/-) mice di splay a high incidence of tumors of the urinary bladder when treated with N -butyl-N-(4-hydroxybutyl)nitrosamine. In the present study, to determine wh ether p53 gene knockout mice can be utilized in a short-term assay model fo r the screening of heterocyclic amines (HCAs), the effects of MeIQx, as a r epresentative compound, at low doses were examined. Male and female p53+/- mice and wild type littermates (p53+/+) were continuously given diets conta ining 0, 0.1, 1, 10 and 100 ppm MeIQx for 1 year. No significant difference in tumor induction was observed other than an increase in liver adenomas i n males receiving 10 ppm MeIQx treatment. The results indicate that p53+/- mice have no practical advantages for use in short-term carcinogenicity tes ts of HCAs, (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.