Genetic control of the induction of gastric tumors by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) was studied in susceptible ACI rats, resistant Buffalo rats, and their F1 and F2 offspring. Both sexes of all strains, initially 7 to 9 weeks old, were given MNNG at a concentration of 83 µg/ml in their drinking water for 32 weeks and were sacrificed at experimental Week 72. The incidence of gastric adenocarcinoma in ACI rats was 80% in males and 47% in females; in Buffalo rats, the incidence was 18% in males and 0% in females. F1 hybrids showed the same resistance to MNNG as did Buffalo rats; the incidence of gastric adenocarcinoma was 17% in males and 8% in females. These results suggest that resistance to induction of gastric adenocarcinoma by MNNG is a dominant characteristic. The incidence of gastric adenocarcinoma in the F2 generation was 36% in males and 14% in females, which is close to the 3:1 ratio expected from the segregation of a single resistant gene. In ACI and Buffalo strains and their hybrids, males were more susceptible than females to induction of gastric carcinoma by MNNG. Intestinal tumors were observed mainly in the duodenum and jejunum in both strains and their hybrids, and the incidences were as follows: ACI: males, 67% and females 42%; Buffalo: males, 12% and females, 18%; F1: males, 18% and females, 15%; and F2: males, 15% and females, 19%. Thus, there seems to be a common genetic basis for both gastric and intestinal carcinogenesis by MNNG.
This work was supported by Grants-in-Aid for Cancer Research from the Ministry of Health and Welfare and the Ministry of Education, Science, and Culture of Japan, and Grants from the Society for Promotion of Cancer Research and the Princess Takamatsu Cancer Research Fund.