Penetration of N-methyl-N'-nitro-N-nitrosoguanidine to proliferative cells in gastric mucosa of rats is different in pylorus and fundus and depends on exposure time and solvent.
We have studied the penetration of a labeled gastric carcinogen, N-(3H)methyl-N'-nitro-N-nitrosoguanidine (3H-MNNG), from the gastric lumen to proliferative cells in the gastric mucosa of Wistar rats. 3H-MNNG was dissolved in deionized water or dimethyl sulfoxide (DMSO) and given intragastrically through a tube in the forestomach. Cells in the S-phase were labeled by incorporation of bromodeoxy-uridine. Penetration of the carcinogen was evaluated by light microscopy after immunohistochemistry and autoradiography. Cells in S-phase labeled with 3H-MNNG (double-labeled cells) are considered to represent the cell population at risk of MNNG-induced carcinogenesis. When deionized water was used as solvent for the carcinogen, the average percentage of double-labeled cells in the pylorus was 12.0, 22.4 and 32.5 respectively, after 10, 30 and 60 min of mucosal exposure to 3H-MNNG. The corresponding percentages for the fundus mucosa were 1.7, 3.1 and 3.4, which are significantly lower than the pylorus values. When DMSO was used as solvent for the carcinogen, the percentage of double-labeled cells was 0.3 and 1.1 in the pylorus and 0.1 and 1.3 in the fundus after 10 and 30 min exposure to 3H-MNNG. Dimethyl sulfoxide caused superficial mucosal damage to the gastric mucosa and increased secretion of fluid into the stomach. Our results strongly suggest that gastric cancer develops in the pylorus because the carcinogen penetrates more easily into pyloric than fundic mucosa. The results support the view that delayed gastric emptying is a risk factor in gastric carcinogenesis, and show that DMSO counteracts the penetration of MNNG into the mucosa.
Department of Surgery, University of Bergen, Haukeland Hospital, Norway.
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Sørbye
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Kvinnsland
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Svanes
D000818:Animals; D001973:Bromodeoxyuridine; D002453:Cell Cycle; D005748:Gastric Fundus; D005753:Gastric Mucosa / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000378:metabolism*; D011706:Pyloric Antrum; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase; D012997:Solvents; D013997:Time Factors; D014316:Tritium
D012997:Solvents; D014316:Tritium; D008769:Methylnitronitrosoguanidine; D001973:Bromodeoxyuridine