Potential tumor-promoting activity of bile acids in rat glandular stomach.
The potential tumor-promoting and -initiating activities of bile acids in the glandular stomach mucosa of F344 rats after administration by gastric intubation were studied. Taurocholic acid sodium salt at doses of 300 to 1200 mg/kg body weight and glycocholic acid sodium salt at doses of 400 to 1200 mg/kg body weight induced up to 100-fold increases in ornithine decarboxylase activity with maxima after 4 hr and up to 10-fold increases in replicative DNA synthesis with maxima after 16-17 hr in the pyloric mucosa of the stomach. Taurodeoxycholic acid sodium salt, taurochenodeoxycholic acid sodium salt and glycocholic acid also induced high ornithine decarboxylase activity, and glycodeoxycholic acid sodium salt and glycochenodeoxycholic acid sodium salt caused slight induction of ornithine decarboxylase activity, but taurolithocholic acid sodium salt did not induce ornithine decarboxylase activity at all in the pyloric mucosa of the stomach. Glycocholic acid sodium salt did not induce unscheduled DNA synthesis in the pyloric mucosa of the stomach. The present results suggest that six bile acids, but not taurolithocholic acid sodium salt, have potential tumor-promoting activities in the pyloric mucosa of rat stomach and that glycocholic acid sodium salt has no potential tumor-initiating activity in the pyloric mucosa of rat stomach.
D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity*; D002273:Carcinogens; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005753:Gastric Mucosa / Q000201:enzymology; D007399:Interphase; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D051381:Rats; D013274:Stomach Neoplasms / Q000139:chemically induced*
D001647:Bile Acids and Salts; D002273:Carcinogens; D004247:DNA; D009955:Ornithine Decarboxylase