Dose, time and route dependency of the induction of rat hepatic ornithine decarboxylase by 12-tetradecanoylphorbol 13-acetate.
Ornithine decarboxylase (ODC) activity, the rate limiting enzyme in polyamine biosynthesis, was determined after 12-O-tetradecanoylphorbol 13-acetate (TPA) administration to female Sprague-Dawley rats. The extent of induction depended on the dose, exposure, time and route of administration. The most effective dose for ODC induction by the intraperitoneal route was 40 ug TPA/kg which caused 3-5 fold ODC induction. Maximal ODC induction occurred in a narrow time band 5 hours after TPA administration. TPA had no adverse effects on hepatic DNA (measured by alkaline elution), cytochrome P-450 content and reduced glutathione content or serum alanine aminotransferase (SGPT) activity.
Mitra
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Toxicology Program, College of Public Health, University of South Florida, Tampa.
Richards
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Kulkarni
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AP
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005978:Glutathione / Q000097:blood; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000633:toxicity*
D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D009955:Ornithine Decarboxylase; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate