Murine epidermal xanthine oxidase activity: correlation with degree of hyperplasia induced by tumor promoters

• Published in: Cancer research (Chicago, Ill.) Ill.), 1987-12, Vol.47 (23), p.6388-6392
• Main Authors: PENCE, B. C, REINERS, J. J. JR
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Carcinogens; Chemical agents; Epidermis - enzymology; Female; Fluocinolone Acetonide - pharmacology; Medical sciences; Mice; Skin Neoplasms - chemically induced; Skin Neoplasms - enzymology; Tetradecanoylphorbol Acetate; Tosylphenylalanyl Chloromethyl Ketone - pharmacology; Tretinoin - pharmacology; Tumors; Xanthine Oxidase - metabolism
• ISSN: 0008-5472; 1538-7445

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.