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Exceptional Activity of Tannic Acid among Naturally Occurring Plant Phenols in Protecting against 7,12-Dimethylbenz(a)anthracene-, Benzo(a)pyrene-, 3-Methylcholanthrene-, and N-Methyl-N-nitrosourea-induced Skin Tumorigenesis in Mice

Departments of Dermatology, University Hospitals of Cleveland and Case Western Reserve University, and the Veterans Administration Medical Center, Cleveland, Ohio 44106

Our recent studies have shown that naturally occurring dietary plant phenols such as tannic acid, quercetin, myricetin, and anthraflavic acid are capable of inhibiting polycyclic aromatic hydrocarbon (PAH) metabolism and subsequent PAH-DNA adduct formation in epidermis of SENCAR mice (M. Das, et al., Cancer Res., 47: 760–766, 1987, and 47: 767–773, 1987). In this study these plant phenols were tested for their effects against PAHs and N-methyl-N-nitrosourea-induced skin tumorigenesis in mice. Each plant phenol was evaluated as a possible anticarcinogen in an initiation and promotion and a complete skin tumorigenesis protocol. In the two-stage tumor protocol in SENCAR mice using 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, and N-methyl-N-nitrosourea as the initiating agent followed by twice weekly applications of 12-O-tetradecanoylphorbol-13-acetate as tumor promoter each plant phenol afforded significant protection against skin tumorigenicity. The protective effects were verified both by prolongation of latency period and by subsequent tumor development. In the complete carcinogenesis protocol in BALB/c mice using 3-methylcholanthrene as a tumorigen the applications of each of the plant phenols 30 min prior to each PAH application afforded significant protection by delaying the onset and the subsequent development of skin tumors. Our results suggest that these plant phenols have substantial though variable potential for modifying the risk of skin tumorigenicity induced by a wide variety of chemicals and of these tannic acid was shown to have maximal chemoprotective effects.

¹ To whom correspondence should be addressed, at Veterans Administration Medical Center, 10701 East Boulevard, Cleveland, OH 44106.

² Present address: Industrial Toxicology Research Centre, P. O. Box 80, Lucknow 226001, India.

Received 9/14/87. Revised 1/15/88. Accepted 1/27/88.

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