Chem.-Btol~ Interactions, 72 (1989) 257-267 257 Elsevier Scientific Publishers Ireland Ltd. SYNERGISTIC INDUCTION OF RAT HEPATIC ORNITHINE DECARBOXYLASE BY MULTIPLE DOSES OF COBALT CHLORIDE SATOSHI NUMAZAWA, TAKIKO OGURO, TAKEMI YOSHIDA and YUKIO KUROIWA Department of Btochemwal Toxicology, School of Pharmaceutwal Sciences, Showa University, 1-5-8 Hatanodat Sh~nagau~, Tokyo 1 ~ (Japan) (Received November 23rd, 1988) (Revision received April 18th, 1989) (Accepted April 18th, 1989) SUMMARY The level of rat hepatic ornithine decarboxylase (0DC) induced by repeti- tive administration of Co2÷ was determined by affinity labeling with [SH]difluoromethylornithine. Such a treatment with Co2÷ ion induced 0DC level to a 10-fold greater extent than single dose of the metal ion or well- known inducers of the enzyme, such as thioacetamide or carbon tetrachloride. The half life of ODC activity induced by repetitive treatment with Co2÷ (95 min) was substantially increased to about 10-fold over the value obtained from the enzyme induced by single treatment with the metal ion (10 min). ODC activity induced by repetitive treatment with Co2÷ was sepa- rated into two peaks by DEAE-Sepharose column chromatography. The two independently collected fractions of ODC peaks exhibited different affinity for pyridoxal 5'-phosphate in vitro and sensitivity to cycloheximide in vivo. Key words: Ornithine decarboxylase - Synergistic induction - Cobalt chloride -- Rat liver INTRODUCTION Naturally occurring polyamines, putrescine, spermidine and spermine, are thought to have an important role for cell growth and differentiation [1,2]. 0rnithine decarboxylase (0DC) which catalyzes the conversion of ornithine to putrescine is the initial and rate-limiting enzyme in the biosynthesis of polyamine. This enzyme has unique properties with respect to its rapid turn- over rate and high inducibility [3,4]. The induction of 0DC is rapid and dra- matic in response to various trophic stimuli including hormones, drugs and Abbreviations: Co 2÷, cobalt chloride; DFMO, difluoromethylornlthme, ODC, ornlthme decarboxy- lase; PLP, pymdoxal 5'-phosphate, TPA, 12-O-tetradecanoylphorbol-13-acetate. 0009-2797/89/$03.50 © 1989 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland