Possible Role of Mucosal Damage in Stomach Carcinogenesis With N- Methyl- N'-Nitro-N-Nitrosoguanidine in the Rat 1,2

SUMMARY-Cytopathic and carcinogenic effects of inter-mittent pulse intragastric administration of saturated solution (5 mgjml) of N-methyl-N '-nitro-N-nitrosoguani-dine (MNNG) on the rat stomach were studied. Degenera-tive changes in the surface epithelium of the glandular stomach and the forestomach were found 1 hour after the intragastric infusion of 2 ml MNNG solution. Deeper cells were also affected and complete erosion was formed in every rat on day 4 after 3 successive doses. After the cessation of MNNG administration, the erosion was re-paired within 4 days. Continuation of this weekly damage-and-repair process rapidly induced gastric cancers. The cancers were in the same mucosal regions where erosion was preferentially formed. The results suggest a role of mucosal damage and its repair in gastric carcinogenesis.-J Natl Cancer Inst 52: 1589-1594, 1974. VARIOUS CARCINOGENIC compounds induce damage and regenerative proliferation of the cells in the target organs. Generally, it has been accepted that repeated tissue damage followed by regeneration provides a favorable condition for carcinogenesis in various experimental systems including skin cancer (1, 2), leukemia (3---5), and hepatoma (6). Recently, Sugimura et a1. (7-10) induced gastric cancers in the glandular stomach of the rat by continuous administration of N-methyl-N '-nitro-N-nitrosoguanidine (MNNG) for over a year. In the present study, we gave the compound intermittently in a higher pulse dose, to induce damage and repair in the gastric mucosa and to observe if such an acute damage-and-repair cycle has any function in the induction of gastric cancers. MATERIALS AND METHODS Male and female Wistar rats, 6 weeks old, were housed 4 to a cage, to which was attached a water flask. They were fed a commercial diet, NM