methylnitronitrosoguanidine and Duodenal-Ulcer

The effect of the duodenal ulceration induced by cysteamine hydrochloride on the development of gastroduodenal tumors initiated by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was studied in F344 rats of both sexes. Cysteamine (200 mg/kg body wt.) was administered by gastric intubation at various times, before, during or after a 16 week period of MNNG (100 mg/liter in drinking water) treatment. In the preliminary experiment, while the ulcers induced were confined to the proximal duodenum, the pyloric region of the stomach also showed slight erosion. Five of 25 male rats given cysteamine 2 weeks before the start of MNNG treatment developed adenocarcinoma in the duodenum as compared to 1 case in the MNNG alone group. In addition, animals of both sexes which received cysteamine during MNNG treatment yielded significantly increased incidences of adenocarcinoma in the pyloric area of the stomach. In line with earlier reports, the present findings suggest that mucosal damage and subsequent regeneration or proliferation of mucosa are important co-factors for MNNG-induced gastroduodenal carcinogenesis in rats.

Topics: Adenocarcinoma; Animals; Cysteamine; Duodenal Neoplasms; Duodenal Ulcer; Female; Male; Methylnitronitrosoguanidine; Rats; Rats, Inbred F344; Stomach Neoplasms

The effect of ulcers on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine in (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 degrees 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 micrograms/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 renewal process that seem to be more responsive to carcinogenic influences that normal cells.

Topics: Adenocarcinoma; Animals; Duodenal Neoplasms; Duodenal Ulcer; Gastric Mucosa; Male; Methylnitronitrosoguanidine; Papilloma; Rats; Stomach Neoplasms; Stomach Ulcer