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 Sprauge-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-mu-g 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.