Gastric mucosa lesions induced by duodenogastric reflux increase penetration of N-[3H]-methyl-N-nitro-N-nitrosoguanidine into corpus mucosa of rats.

The mucosal changes by which duodenogastric reflux may predispose to gastric cancer have not been fully clarified. In this study in rats, duodenal fluid was directed into the stomach through a gastroenterostomy (jejunal reflux, N = 29) or through the pylorus (pyloric reflux, N = 30) and compared with 30 controls. Twenty-four weeks later the stomach was exposed to N-[3H]methyl-N-nitro-N-nitrosoguanidine ([3H]MNNG). The corpus mucosa was examined for proliferating cells (bromodeoxyuridine labeled) and cells at risk of methyl-N-nitro-N-nitrosoguanidine-induced carcinogenesis (cells labeled with bromodeoxyuridine and [3H]MNNG). The number of double-labeled cells increased from 0.8 +/- 0.1/mm mucosa in the control group to 5.2 +/- 0.9 in the jejunal reflux group (P < 0.05) and 2.7 +/- 0.5 in the pyloric reflux group (P < 0.05). An erosion or ulcer appeared at the gastroenterostomy in 52% of animals with jejunal reflux and 17% of those with pyloric reflux (P < 0.006). Within erosions the mean number of double-labeled cells was 9.6 +/- 2.2 in the jejunal reflux group and 7.7 +/- 4.8 in the pyloric reflux group, and significantly higher than in the nonlesion area of the mucosa (0.6 +/- 0.2 and 0.8 +/- 0.3). In erosions the distance between the gastric lumen and the proliferating cells was significantly shorter and the cell proliferation significantly higher than in the nonlesion area of the mucosa. We conclude that duodenogastric reflux increases the penetration of [3H]MNNG into the corpus mucosa of rats and also induces mucosa lesions, which further increase the penetration of [3H]MNNG into the corpus mucosa.