Duodenogastric Reflux Increases the Penetration of N‐³H‐Methyl‐N‐nitro‐N‐nitrosoguanidine into the Antral Mucosa of Rats: A Possible Role for Mucosal Erosions and Increased Cell Proliferation in Gastric Carcinogenesis

Abstract

Duodenogastric reflux is a risk factor for gastric carcinogenesis, but the pathogenesis is not fully understood. We studied the risk of N-methyl-N-nitro-N-nitrosoguanidine (MNNG)-induced carcinogenesis in the antrum of rats with duodenogastric reflux. Duodenal fluid was directed into the stomach through the pylorus (pyloric reflux group) or through a gastrojejunostomy (jejunal reflux group). After twenty-four weeks, 5-bromo-2-deoxyuridine (BrdU) was injected intravenously and the stomach was exposed to N-3 H-methyl-N-nitro-N-nitrosoguanidine ( 3 H-MNNG). The antral mucosa was examined with immunohistochemistry and autoradiography for identification of proliferating cells (BrdU labelled) and cells at risk of MNNG-induced carcinogenesis ( 3 H-MNNG and BrdU-labelled cells). Duodenogastric reflux increased the number of double-labelled cells in the antral mucosa from 4.8 ± ± ± ±0.6 per mm in the control group to 11.3 ± ± ± ±1.9 in the jejunal reflux group (P < < < <0.05) and 12.7 ± ± ± ±0.9 in the pyloric reflux group (P < < < <0.05). Mucosal erosions were observed in 15 of 28 animals with pyloric reflux and the number of double-labelled cells in the erosion area (4.3 ± ± ± ±0.7) was higher than in the same area of animals without erosion (1.4± ± ± ±0.5) (P < < < <0.05). Duodenogastric reflux increased the cell proliferation and significantly changed the distance between the surface epithelial lining and the proliferating cells when compared to the controls. These results indicate that duodenogastric reflux increases the penetration of 3 H-MNNG into the antrum mucosa of rats. Increased cell proliferation and erosions increase the number of cells at risk of an initiation process from a penetrating gastric carcinogen.Key words: Methylnitronitrosoguanidine -Duodenogastric reflux -Stomach neoplasms -Gastric mucosa -Mucosa erosion Duodenogastric reflux is one of several risk factors for gastric carcinogenesis.1) Other risk factors are Helicobacter pylori (Hp) infection and smoking, 2, 3) which also increase duodenogastric reflux. 4,5) Increased levels of bile acids have also been observed in stomachs with atrophic gastritis, intestinal metaplasia and dysplasia. 6,7) Experiments in rats confirm that duodenogastric reflux induces gastric cancer without addition of exogenous carcinogens. 8) However, increased gastric levels of N-nitroso compounds in patients with a resected stomach suggest that duodenogastric reflux favours a milieu for conversion of nitrite to possible carcinogenic substances. 9)The effect of duodenogastric reflux on gastric carcinogenesis has been studied mostly in the corpus of animals with resected antrum. [10][11][12] The documentation for a role of duodenogastric reflux in carcinogenesis of the antrum is therefore scanty. 8,13) Taurocholic acid supplied in the food to mimic duodenogastric reflux after a period of initiation with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) increases the tumour yield both in the antrum and in the corpus mucosa of rats.14)The mucosal changes by which duodenogastric reflux...

Correlation of precancerous lesion incidence with duodenogastric reflux and N-nitroso compound duration at reflux and antireflux stomach surgery: An experimental study

“…Øvrebø et al 20 , concluded that the superficial part of the mucosa, triggered by DGR, i.e., by billiary salts, further supports the penetration of MNNG in the proliferative gastric mucosa part.…”