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Inhibition of 12-O-Tetradecanoylphorbol-13-acetate-caused Tumor Promotion in 7,12-Dimethylbenz[a]anthracene-initiated SENCAR Mouse Skin by a Polyphenolic Fraction Isolated from Green Tea¹

Department of Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, and Department of Veterans Affairs Medical Center, Cleveland, Ohio 44106

² To whom requests for reprints should be addressed, at the Department of Veterans Affairs Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

Our laboratory has been studying cancer chemopreventive effects of polyphenolic fraction isolated from green tea (GTP). In prior studies we have shown that (a) GTP possesses antigenotoxic effects in various test systems; (b) topical application of GTP protects against UV radiation and chemical carcinogen-induced tumorigenesis in murine skin; and (c) feeding of GTP in drinking water p.o. to mice protects against carcinogen-induced forestomach and lung tumorigenesis. Recently, we showed that in a dose-dependent manner GTP inhibits tumor promoter-caused induction of epidermal ornithine decarboxylase activity in SENCAR mice (R. Agarwal et al., Cancer Res., 52: 3582–3588, 1992). In the present study, we assessed the effect of GTP on TPA-induced skin tumor promotion in 7,12-dimethylbenz(a)anthracene-initiated SENCAR mouse. Topical application of varying doses of GTP (1–24 mg) 30 min prior to that of each TPA application resulted in highly significant protection against skin tumor promotion in a dose-dependent manner. The animals pretreated with GTP showed substantially lower tumor body burden such as decrease in total number of tumors per group, number of tumors per animal, tumor volume per mouse, and average volume per tumor, as compared to the animals that did not receive GTP. Since TPA-induced epidermal cyclooxygenase and lipoxygenase activities and edema and hyperplasia are conventionally used markers of skin tumor promotion, we also assessed the effect of preapplication of GTP on these parameters. As quantitated by the formation of prostaglandin and hydroxy-eicosatetraenoic acid metabolites from, respectively, cyclooxygenase- and lipoxygenase-catalyzed metabolism of arachidonic acid, skin application of GTP to SENCAR mice resulted in significant inhibition of TPA-caused effects on these 2 enzymes. Prior application of GTP to mouse skin also resulted in 30–46% inhibition of TPA-induced epidermal edema and hyperplasia. The results of the present study suggest that GTP possesses anti-skin tumor-promoting effects, and that the mechanism of such effects may involve inhibition of tumor promoter-induced epidermal ornithine decarboxylase, cyclooxygenase and lipoxygenase activities, edema, and hyperplasia. Further studies are in progress to define which component present in GTP is responsible for its anti-skin tumor-promoting effects.

¹ This work is supported by USPHS Grants ES-1900 and P-30-AR-39750, American Institute for Cancer Research Grant 90A47, and by research funds from the Department of Veterans Affairs. R. A. is a recipient of a Dermatology Foundation Research Grant Award. Portions of this work were presented at the 83rd Annual Meeting of the the American Association of Cancer Research, San Diego, CA, 1992 (Proc. Am. Assoc. Cancer Res., 33: 168, 1992).

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 6/25/92. Accepted 10/ 2/92.

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