Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters.
Topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to SENCAR mouse skin results within 48 h in a 3-fold elevation of xanthine oxidase (XO) activity, an enzyme capable of generating the reactive oxygen species superoxide and hydrogen peroxide. The antiinflammatory steroid fluocinolone acetonide, an inhibitor of TPA-induced hyperplasia, as well as the multiple stages of tumor promotion as defined in SENCAR mice (Stages I and II), inhibited the TPA-dependent elevation of epidermal XO activity. Neither tosylphenylalanyl chloromethyl ketone nor retinoic acid, inhibitors of promotion Stages I and II, respectively, had significant effects on TPA-induced hyperplasia or elevated XO activity. The nonpromoting but hyperplasiogenic agents ethyl phenylpropiolate and acetic acid significantly elevated XO activity within 48 h of topical application. The non-phorbol ester tumor promoter benzoyl peroxide also elevated XO activity consistent with the degree of induced hyperplasia. Multiple treatments with TPA or ethyl phenylpropiolate resulted in a sustained elevation of XO activity which peaked at five treatments and then declined. Sustained inhibition of XO activity by p.o. administration of allopurinol did not inhibit the TPA-induced hyperplasia as determined histologically. These results suggest that the TPA-dependent elevation of epidermal XO activity is associated with the hyperplasia induced by the agent, and is a consequence of the hyperplasia rather than the cause of it.
Pence
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BC
University of Texas System Cancer Center, Science Park--Research Division, Smithville 78957.
Reiners
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JJ
D000818:Animals; D002273:Carcinogens; D004817:Epidermis / Q000201:enzymology*; D005260:Female; D005446:Fluocinolone Acetonide / Q000494:pharmacology; D051379:Mice; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology; D013755:Tetradecanoylphorbol Acetate; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000378:metabolism*
D002273:Carcinogens; D005446:Fluocinolone Acetonide; D014108:Tosylphenylalanyl Chloromethyl Ketone; D014212:Tretinoin; D014969:Xanthine Oxidase; D013755:Tetradecanoylphorbol Acetate