Attenuating effect of ornithine decarboxylase inhibitor (1,3-diaminopropane) on bombesin enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.
The effects of combined administration of bombesin and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric tumors induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the ODC activity of the gastric wall and the labelling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water containing MNNG (50 micrograms/ml) for 25 weeks and then drinking water containing DAP (2.5 g/l) and/or injections of 40 micrograms/kg body weight of bombesin in depot form every other day. Administration of bombesin alone resulted in significant increases in the incidence of gastric cancers, the ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Administration of DAP with bombesin significantly reduced enhancement by the latter of gastric carcinogenesis, ODC activity of the antral portion of the gastric wall and the labelling index of the antral mucosa. Our results suggest that ODC inhibition attenuated the enhancement of gastric carcinogenesis by bombesin, and that this enhancement by bombesin was mediated by polyamine biosynthesis.
Iishi
H
H
Department of Gastrointestinal Oncology, Center for Adult Diseases, Osaka, Japan.
Tatsuta
M
M
Baba
M
M
Okuda
S
S
Taniguchi
H
H
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000201:enzymology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D003959:Diamines / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D005753:Gastric Mucosa / Q000378:metabolism; D005755:Gastrins / Q000097:blood; D006863:Hydrogen-Ion Concentration; D008297:Male; D008769:Methylnitronitrosoguanidine; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000201:enzymology
D003959:Diamines; D005755:Gastrins; D065108:Ornithine Decarboxylase Inhibitors; D008769:Methylnitronitrosoguanidine; C009475:trimethylenediamine; D001839:Bombesin