Ornithine decarboxylase inhibitor lessens the rat gastric carcinogenesis enhancement caused by tyrosine methyl ester.
The effects of combined administration of a catecholamine precursor, tyrosine methyl ester (TME), and an ornithine decarboxylase (ODC) inhibitor, 1,3-diaminopropane (DAP), on the incidence of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the norepinephrine (NE) concentration and ODC activity of the gastric wall, and the labeling index of the gastric mucosa were investigated in inbred Wistar rats. Rats received s.c. injections of TME, 512 mg/kg body weight, every other day and drinking water with or without 2.5 g/l of DAP after 25 weeks of oral administration of MNNG. At week 52, administration of TME resulted in significant increases in the incidence of gastric cancers, in the NE concentration and the ODC activity of the antral portion of the gastric wall, and in the labeling index of antral epithelial cells. Administration of both TME and DAP significantly reduced the enhancements by TME of gastric carcinogenesis, NE concentration and ODC activity of the antral wall, and the labeling index of the antral mucosa. Our results suggest that ODC inhibition lessens enhancement by TME of gastric carcinogenesis and that the enhancement by TME of gastric carcinogenesis is mediated in part by polyamine biosynthesis.
Iishi
H
H
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan.
Tatsuta
M
M
Baba
M
M
Yano
H
H
Sakai
N
N
Uehara
H
H
Nakaizumi
A
A
D000818:Animals; D003959:Diamines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D008769:Methylnitronitrosoguanidine; D009638:Norepinephrine / Q000032:analysis; D009955:Ornithine Decarboxylase / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000633:toxicity
D003959:Diamines; D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; C040444:tyrosine methyl ester; D008769:Methylnitronitrosoguanidine; D014443:Tyrosine; C009475:trimethylenediamine; D009955:Ornithine Decarboxylase; D009638:Norepinephrine