Susceptibilities of p53 knockout and rasH2 transgenic mice to urethane-induced lung carcinogenesis are inherited from their original strains.

In the present study, susceptibility of CB6F1 mice carrying the human prototype c-Ha-ras gene (rasH2 mice) and p53 gene knockout mice (p53 (+/-) mice) to urethane-induced lung carcinogenesis was compared under the same experimental conditions. Both strains were administered 500 ppm urethane in their drinking water for 3 weeks. At week 26, lung adenocarcinomas and adenomas were observed in 53% and 100% of rasH2 mice, respectively, and lung adenomas were observed in 67% of rasH2 littermate (non-Tg) mice. However, lung tumors were not observed in either p53 (+/-) or p53 (+/+) mice. Peliosis hepatis and hepatic hemangiomas were observed in 27% and 67% of p53 (+/-) mice, but only in 6.7% and 6.7% of the rasH2 animals, respectively. Under the same experimental conditions, BALB/c mice, the strain of origin of the rasH2 mice, developed lung adenomas at an incidence of 93%, whereas none of the C57BL/6 original strain for p53 (+/-) mice developed lung tumors. Peliosis hepatis was observed in 40% of the C57BL/6 mice, but not in BALB/c mice; hepatic and splenic hemangiomas were not observed in these animals. These results indicate that organ susceptibility of rasH2 and p53 (+/-) mice is inherited from their strains of origin, the rasH2 and BALB/c lines being much more sensitive to the induction of pulmonary carcinogenesis.