EFFECT OF COLCHICINE ON INDUCTION OF ORNITHINE DECARBOXYLASE BY 12-O-TETRADECANOYL-PHORBOL-13-ACETATE

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 36  (10) , 3766-3770
Abstract
The induction of mouse epidermal ornithine decarboxylase, one of the earliest and largest phenotypic changes following treatment of mouse skin with the tumor promoting agent, 12-O-tetradecanoyl-phorbol-13-acetate, can be inhibited by prior administration of colchicine. Maximal inhibition of this enzyme induction was observed when colchicine was injected i.p. 90 or 120 min before promoter treatment, although time intervals up to 20 h between colchicine and promoter treatment were effective. The effect of colchicine was dose dependent, with a dose as low as 25 nmol/mouse causing an inhibition of 35%. Other microtubule disrupting agents, vinblastine, vincristine and Colcemid, had a similar effect on ornithine decarboxylase activity. .beta.,.gamma.-Lumicolchicine, a photochemical derivative of colchicine with no antimitotic or microtubule disrupting ability, and cytochalasin B, an inhibitor of microfilament dependent processes, had no effect. N6,O2''-dibutyryl cyclic [c]AMP, when administered just before colchicine, blocked the inhibitory action of colchicine. Colchicine sensitive structures, most likely containing microtubules, may be mediating elements between the binding of tumor promoters, perhaps to specific cell surface receptors, and the subsequent induction of ornithine decarboxylase.