Inhibition of mouse skin tumor promotion and of promoter-induced epidermal polyamine biosynthesis by methylglyoxal bis(butylamidinohydrazone)

Effects of methyiglyoxal bis(butylamidinohydrazone) (MGBB),a reversible inhibitor of ornithine decarboxylase (ODC) andS-adenosylmethionine decarboxylase (AdoMetDC), on 12-0-tetradecanoylphorbol-13-acetate(TPA)-induced increases of ODC and AdoMetDC activities, ODCmRNA level and polyamine contents in mouse skin were investigatedin connection with tumor formation. Formation of papillomasby applications of TPA to 7,12-dimethylbenz[a]anthracene (DMBA)-initiatedmouse skin was effectively inhibited by simultaneous topicalapplications of MGBB. MGBB also dose-dependently inhibited theability of TPA to induce increases of ODC activity, ODC mRNAlevel and the accumulation of putrescine and spermidine in mouseskin. Induction of AdoMetDC activity was not affected by thedrug. These inhibitory effects of MGBB on ODC induction andtumor promotion were more evident in multiple application experimentsthan with a single application of the drug.