The induction of ornithine decarboxylase by phorbol 12-myristate 13-acetate or by serum is inhibited by antioxidants.
The mechanism of action of tumor promoters may involve the modulation of gene expression, e.g., the induction of ornithine decarboxylase (ODC). The tumor promoter phorbol-13-myristate-12-acetate (PMA) induces chromosomal damage via the intermediacy of active oxygen species which may trigger the activation of certain genes. Therefore, we have studied the effect of antioxidants on the induction of ODC by PMA, medium change only and medium change plus PMA in mouse mammary tumor cells Mm5mt/C1. CuZn-superoxide dismutase (SOD, a scavenger of superoxide radicals), catalase (CAT, a scavenger of hydrogen peroxide) and mannitol (a scavenger of hydroxyl radicals) suppressed ODC induction under all three conditions. The relative inhibitory potency of the antioxidants was always SOD less than CAT less than mannitol less than SOD + CAT. Maximal suppression by SOD + CAT was approximately 50%. It is concluded that active oxygen species play a role in ODC induction by factors contained in serum and by PMA.
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001769:Blood; D002374:Catalase / Q000494:pharmacology*; D002460:Cell Line; D003470:Culture Media; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007700:Kinetics; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology; D051379:Mice; D008809:Mice, Inbred C3H; D009955:Ornithine Decarboxylase / Q000235:genetics*; D010704:Phorbols / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000975:Antioxidants; D003470:Culture Media; D010704:Phorbols; D002374:Catalase; D013482:Superoxide Dismutase; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate