Ulcer Formation and Associated Tumor Production in Multiple Sites Within the Stomach and Duodenum of Rats Treated With N-Methyl-N-nitro-N-nitrosoguanidine23
The effect of ulcers on the development of gastric tumors by N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) was studied in male Wistar rats. Ulcers were produced by the application of a steel rod, 5 mm in diameter and frozen at −78°C, to the serosal surface of the forestomach, fundus, pylorus, or proximal duodenum. The existence of the ulcers at these areas was confirmed 1 week later in a preliminary experiment. Experimental groups were given MNNG in their drinking water at a concentration of 100 pg/ml for 16 weeks beginning 7 days after the ulcers developed. Administration of MNNG after ulceration resulted in a relative increase in the tumor incidences at each ulcer site, especially the proximal duodenum, which suggested that regenerating cells in the duodenum were the most susceptible cells among the cells of the four sites. The increase in tumor incidence following ulceration may be due to exposure of MNNG to a greater number of regenerating cells during the renewalprocess that seem to be more responsive to carcinogenic influences than normal cells.