Degree of Hyperplasia Induced by Tumor Promoters Murine Epidermal Xanthine Oxidase Activity: Correlation with

Topical application of the tumor promoter 12-0-tetradecanoylphorbol13-acetate (TPA) to SENCAR mouse skin results within 48 h in a 3-fold elevation of xanthine oxidase (XO) activity, an enzyme capable of gen erating the reactive oxygen species Superoxide and hydrogen peroxide. The antiinflammatory steroid fluocinolone acetonide, an inhibitor of TPAinduced hyperplasia, as well as the multiple stages of tumor promotion as defined in SENCAR mice (Stages I and II), inhibited the TPAdependent elevation of epidermal XO activity. Neither tosylphenylalanyl chloromethyl ketone nor retinole 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 phenylpro piolate 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 hyper plasia as determined histologically. These results suggest that the TPAdependent 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.