Lack of Carcinogenic Sensitivity of the Glandular Stomach in Heterozygous p53 Knockout Mice Given N-Methyl-N-Nitrosourea in their Drinking Water for 26 Weeks

Abstract

Gastric tumorigenic sensitivity to N-methyl-N-nitrosourea (MNU) was examined in heterozygous p53 knockout ‍(p53(+/-)) CBA mice and their wild-type littermates (p53(+/+)). In Experiment 1, 37 male p53(+/-) or 38 male p53(+/ ‍+) CBA mice were given MNU in their drinking water at concentration of 50ppm (Group 1 or 4), 10ppm (group 2 or ‍5) or 0ppm (group3 or 6) for 26 weeks. In Experiment 2, p53(+/-) and p53(+/+) CBA mice of both sexes received ‍water containing 50ppm MNU for 26 weeks. In Experiment 1, the incidences of hyperplasias in the glandular ‍stomach observed in p53 (+/-) CBA mice treated with 50ppm and 10ppm MNU were significantly increased, as ‍compared with the control group. No tumors were induced in the stomach of any treated groups. Some proliferative ‍or non-neoplastic lesions were observed in some p53 (+/-) CBA mice, but there was no significant difference in their ‍incidences between treated and control groups. In Experiment 2, the incidences of hyperplasias in the glandular ‍stomach observed in p53 (+/-) CBA mice of both sexes treated with 50ppm MNU were not significantly increased, as ‍compared with the treated p53(+/+) CBA group. One papilloma of the forestomach was observed only in a male ‍p53(+/-) CBA mouse treated with 50ppm MNU. The present study suggests that p53 (+/-) CBA mice have low ‍susceptibility to MNU-induced gastic carcinogenesis.