Inhibition of ultraviolet-B epidermal ornithine decarboxylase induction and skin carcinogenesis in hairless mice by topical indomethacin and triamcinolone acetonide.
Modulation of ultraviolet-B (UVB) skin carcinogenesis by topical treatment with two antiinflammatory drugs expected to have different mechanisms of action has been studied in the hairless mouse. Indomethacin is a nonsteroidal antiinflammatory agent which may act by inhibiting prostaglandin biosynthesis. Triamcinolone acetonide is a steroidal antiinflammatory agent. Both of these drugs inhibited the induction of epidermal ornithine decarboxylase by UVB when applied topically in a acetone vehicle. A UVB skin tumor study was designed. Groups of mice were irradiated daily with UVB for 20 days, each mouse receiving a total of 17.1 kJ UVB per sq m. Group 1 was treated with acetone immediately after each irradiation; Group 2 received 700 nmol indomethacin in acetone immediately after each irradiation; Group 3 received 14.4 nmol triamcinolone acetonide in acetone immediately after each irradiation. Mice were killed after 52 weeks, and the tumors were excised and examined histologically. Both topical indomethacin and topical triamcinolone acetonide were effective in reducing the incidence and size of the skin tumors induced by UVB. This evidence supports the hypothesis that the induction of ornithine decarboxylase may be a critical component of UVB skin carcinogenesis and that inhibition of ornithine decarboxylase induction can be used as a screen for agents which will inhibit UVB skin carcinogenesis.
D000818:Animals; D002262:Carboxy-Lyases / Q000235:genetics*; D002273:Carcinogens; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009374:Neoplasms, Experimental / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000473:pathology*; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000528:radiation effects; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology; D014221:Triamcinolone / Q000494:pharmacology*; D014466:Ultraviolet Rays
D002273:Carcinogens; D014221:Triamcinolone; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D007213:Indomethacin