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Mechanism of Mouse Skin Tumor Promotion by Chrysarobin¹

The Wistar Institute, Philadelphia, Pennsylvania 19104 [P. C. D., W. P. P., J. C.], The University of Texas System Cancer Center, Science Park—Research Division, Smithville, Texas 78957 [J. D., K. K. A.]; and The Imperial Cancer Research Fund, P. O. Box No. 123, Lincoln's Inn Fields, London, WC2A 3PX England [M. M. C.]

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 to 2 times more potent than anthralin. Maximal papilloma responses were achieved by 15 weeks of promotion with TPA whereas at least 25 weeks of promotion were necessary to achieve maximal papilloma responses with chrysarobin or anthralin indicating marked differences in tumor latency between the two classes of compounds. Interestingly, at optimal promoting doses, chrysarobin gave a carcinoma response (22% with 0.3 carcinomas per mouse at 45 weeks) similar to that of TPA suggesting that this compound may be more efficient at promoting carcinomas than papillomas. In two-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: (a) skin edema, (b) epidermal hyperplasia, and (c) epidermal omithine decarboxylase. In each case, distinct differences were noted between the two compounds. When taken together, the data support the hypothesis that anthracene-derived skin tumor promoters work at least in part by a mechanism different from the phorbol esters.

¹ Research supported in part by NIH Grants CA 10815, CA 33403, and CA 37111. A portion of this work was conducted at the University of Texas System Cancer Center, Science Park—Research Division, Smithville, TX 78957.

² To whom requests for reprints should be addressed.

Received 9/24/84. Revised 2/13/85. Accepted 2/14/85.

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