Inhibition by Putrescine of the Induction of Epidermal Ornithine Decarboxylase Activity and Tumor Promotion Caused by 12-O- Tetradecanoylphorbol-13-acetate1
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چکیده
The induction of epidermal ornithine decarboxylase (EC 4.1.1.17) (ODC) following topical application of the tumorpromoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) to mice can be inhibited by topical application of putrescine, the product of the enzyme. The degree of inhibition depended on both the dose and the time of putrescine application; appli cation of 20 jumol of putrescine 2 hr after TPA treatment inhibited the induction of ODC activity by 50%. TPA-induced activity of another polyamine-biosynthetic enzyme, S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50), was unaffected by application of putrescine. Among several amines tested for their ability to inhibit the induction of ODC activity, spermidine, 1,7-diaminoheptane, and spermine were the most effective, causing a 90% inhibition at the 20-jumol dose. Putrescine, when added directly to the assay medium at a 100-^mol dose level inhibited by 97% the TPA-induced ODC activity, but the amount of putrescine (20 /^mol) which gave 50% inhibition of the induction of ODC activity in vivo had no effect when added to the assay system. Mixing of soluble extracts from TPA-treated mouse epidermis posttreated either with acetone or putrescine or with mouse epidermis treated with putrescine alone gave essentially additive ODC activity. Furthermore, putrescine did not elicit production of detectable ODC-antizyme activity in mouse epidermis. Putrescine inhibited the formation of mouse skin papillomas promoted with TPA. Topical application of 20 and 100 /umol of putrescine 2 hr after each application of TPA to mice initiated with 7,12-dimethylbenz[a]anthracene resulted in a 30 and 80% inhibition, respectively, of papilloma formation compared to animals receiving no putrescine.
منابع مشابه
Ornithine decarboxylase activity, cell proliferation, and tumor promotion in mouse epidermis in vivo.
The effect of different phorbol esters and of mechanical treatment on the activity of ornithine decarboxylase in mouse epidermis in vivo was investigated. The strong promoter 12-O-tetradecanoylphorbol-13-acetate as well as the weak promoters phorbol dibenzoate and the 12-O-tetradecanoylphorbol-13-acetate analog 12-O-tetradeca-2-cis, 4-trans-6,8-tetraenoylphorobol-13-acetate strongly increased t...
متن کاملInhibition by putrescine of the induction of epidermal ornithine decarboxylase activity and tumor promotion caused by 12-O-tetradecanoylphorbol-13-acetate.
The induction of epidermal ornithine decarboxylase (EC 4.1.1.17) (ODC) following topical application of the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) to mice can be inhibited by topical application of putrescine, the product of the enzyme. The degree of inhibition depended on both the dose and the time of putrescine application; application of 20 mumol of putrescine 2 hr ...
متن کاملInhibition of 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion and epidermal ornithine decarboxylase activity in mouse skin by palmitoylcarnitine.
Palmitoylcarnitine, which has been reported to be an inhibitor of calcium-activated, phospholipid-dependent protein kinase (protein kinase C), inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced epidermal ornithine decarboxylase in mouse skin in a dose-dependent manner. Neither acetylcarnitine nor palmitic acid inhibited TPA-caused ornithine decarboxylase induction. In addition, palmit...
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Application of the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin leads to a manifold induction of ornithine decarboxylase (ODC) activity within 5 hr and an increased accumulation of putrescine. The relevance of these TPA-induced changes to the mechanism of tumor promo tion was investigated using a-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC....
متن کاملEffects of single applications of 12-O-tetradecanoylphorbol-13-acetate, mezerein, or ethylphenylpropiolate on DNA synthesis and polyamine levels in hairless mouse epidermis.
Quantitative and qualitative changes in epidermal polyamine levels and DNA synthesis (specific activity and labeling index) after a single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA), mezerein (MEZ), or ethylphenylpropiolate (EPP) in acetone were studied concomitantly in the same epidermal cell population from each treated mouse. The doses tested were 17 nmol of TPA; 1.7, ...
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تاریخ انتشار 2006