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 p 53 knockout(p 53(+/-)) CBA mice and their wild-type littermates ( p 53(+/+)). In Experiment 1, 37 male p 53(+/-) or 38 male p 53(+/+) CBA mice were given MNU in their drinking water at concentration of 50ppm (Group 1 or 4), 10ppm (group 2 or5) or 0ppm (group3 or 6) for 26 weeks. In Experiment 2, p 53(+/-) and p 53(+/+) CBA mice of both sexes receivedwater containing 50ppm MNU for 26 weeks. In Experiment 1, the incidences of hyperplasias in the glandularstomach observed in p 53 (+/-) CBA mice treated with 50ppm and 10ppm MNU were significantly increased, ascompared with the control group. No tumors were induced in the stomach of any treated groups. Some proliferativeor non-neoplastic lesions were observed in some p 53 (+/-) CBA mice, but there was no significant difference in theirincidences between treated and control groups. In Experiment 2, the incidences of hyperplasias in the glandularstomach observed in p 53 (+/-) CBA mice of both sexes treated with 50ppm MNU were not significantly increased, ascompared with the treated p 53(+/+) CBA group. One papilloma of the forestomach was observed only in a malep 53(+/-) CBA mouse treated with 50ppm MNU. The present study suggests that p 53 (+/-) CBA mice have lowsusceptibility to MNU-induced gastic carcinogenesis.Key words : heterozygous p53 deficient CBA mouse - carcinogen sensitivity - glandular stomach - N-methyl-N-nitrosourea