MECHANISM OF MOUSE SKIN TUMOR PROMOTION BY CHRYSAROBIN

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  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (6) , 2584-2589
Abstract
The skin tumor-promoting ability of 1,8-dihydroxy-3-methyl-9-anthrone (chrysarobin) was compared with that of 12-O-tetradecanoylphorbol-13-acetate (TPA) and 1,8-dihydroxy-9-anthrone (anthralin) in SENCAR mice. Although dose-response comparisons indicated that chrysarobin was several orders of magnitude less potent than TPA for promoting papilloma formation, this anthrone was 1.5-2 times more potent than anthralin. Maximal papilloma responses were achieved by 15-wk of promotion with TPA whereas at least 25 wk of promotion were necessary to achieve maximal papilloma responses with chrysarobin or anthralin indicating marked differences in tumor latency between the 2 classes of compounds. Interestingly, at optimal promoting doses, chrysarobin gave a carcinoma response (22% with 0.3 carcinomas per mouse at 45 wk) similar to that of TPA suggesting that this compound may be more efficient at promoting carcinomas than papillomas. In 2-stage promotion experiments, chrysarobin was incapable of functioning independently as a Stage I or II promoter despite its complete promoting activity. Chrysarobin and TPA were compared at optimal promoting doses for their ability to induce: skin edema, epidermal hyperplasia and epidermal ornithine decarboxylase. In each case, distinct differences were noted between the 2 compounds. The hypothesis that anthracene-derived skin tumor promoters work at least in part by a mechanism different from the phorbol esters was supported.