title: 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). Duodeno-gastric 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.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Bergen, Haukeland Hospital, N-5021 Bergen, Norway. Kjell.Ovrebo@kir.uib.no
authors.forename: Kjell K
authors.initials: KK
authors.lastname: Øvrebø
authors.forename: Knut
authors.initials: K
authors.lastname: Svanes
authors.forename: Steinar
authors.initials: S
authors.lastname: Aase
authors.forename: Ketil
authors.initials: K
authors.lastname: Grong
authors.forename: Halfdan
authors.initials: H
authors.lastname: Sørbye
mesh_terms: D000818:Animals; D001652:Bile Ducts / Q000033:anatomy & histology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002273:Carcinogens; D002455:Cell Division; D004383:Duodenogastric Reflux / Q000150:complications*; D005753:Gastric Mucosa / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D008769:Methylnitronitrosoguanidine; D010183:Pancreatic Ducts / Q000033:anatomy & histology; D051381:Rats; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D013997:Time Factors
chemical_list: D002273:Carcinogens; D008769:Methylnitronitrosoguanidine; D001973:Bromodeoxyuridine