Ornithine decarboxylase inhibitor attenuates NaCl enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine.
The effects of combined administration of NaCl and the ornithine decarboxylase (ODC) inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and on the ODC activity of the gastric wall and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats were given drinking water with or without 2.5 g/l DAP and chow pellets with and without 10% NaCl ad libitum after 25 weeks of oral administration of MNNG. At week 52 feeding 10% NaCl resulted in significant increases in the incidence of gastric cancers, in the ODC activity of the antral portion of the gastric wall and in the labeling index of antral epithelial cells. Administration of both NaCl and DAP significantly reduced the enhancements by NaCl of gastric carcinogenesis, ODC activity of the antral wall and the labeling index of antral epithelial cells. These results suggest that inhibition of ODC attenuates NaCl enhancement of gastric carcinogenesis and that enhancement by NaCl of gastric carcinogenesis is mediated by polyamine biosynthesis.
Tatsuta
M
M
Department of Gastrointestinal Oncology, Centre for Adult Diseases, Osaka, Japan.
Iishi
H
H
Baba
M
M
Yano
H
H
Uehara
H
H
Nakaizumi
A
A
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D003959:Diamines / Q000633:toxicity*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000633:toxicity*; D013270:Stomach / Q000187:drug effects / Q000201:enzymology; D013274:Stomach Neoplasms / Q000139:chemically induced* / Q000473:pathology
D002273:Carcinogens; D003959:Diamines; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D008769:Methylnitronitrosoguanidine; D012965:Sodium Chloride; C009475:trimethylenediamine; D009955:Ornithine Decarboxylase