Susceptibility of healed gastric ulcers to chemical carcinogenesis in rats and implications of cellular kinetic changes.
The susceptibility of healed, experimental gastric ulcers to chemical carcinogenesis was investigated. Slowly healing gastric ulcers were induced by the acetic acid method in the fundic and pyloric gastric mucosae of inbred male Wistar rats. N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) was administered in drinking water at a concentration of 50 mg/liter for 360 days after ulcer induction. Twenty-eight adenomatous hyperplasias and six-adenocarcinomas developed in the pyloric mucosae of rats, including five cases of adenomatous hyperplasia which developed in the periphery of the healed ulcer. In contrast, only one adenomatous lesion was found in the regenerated mucosa of the healed pyloric ulcer. No neoplasm was observed in the healed fundic ulcer area. The results demonstrated an increased incidence of neoplasms in the peripheral area of the healed pyloric ulcer and a decreased incidence of neoplasms in the regenerated mucosa within the healed pyloric ulcer scar, although these differences were not statistically significant in comparison with the intact pyloric mucosae of the MNNG-treated rats. Histoautoradiographs of the gastric mucosae demonstrated increased labeling indices in the healed ulcer periphery of the pyloric mucosa and decreased labeling indices in the regenerated mucosa within the healed pyloric ulcer scar of MNNG-treated rats, which might be related to the differential susceptibility of the two regions to gastric carcinogenesis. Intestinal metaplasia preferentially developed near the pyloroduodenal junction in MNNG-treated rats but was not localized in control rats. In the fundic ulcer scar area, an unusual squamous cell metaplasia was observed in one rat.
D000818:Animals; D002455:Cell Division; D004198:Disease Susceptibility; D005753:Gastric Mucosa / Q000473:pathology; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity; D011706:Pyloric Antrum / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D013276:Stomach Ulcer / Q000150:complications / Q000473:pathology*; D014945:Wound Healing
D008769:Methylnitronitrosoguanidine