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Promotion-like Enhancement of Tracheal Carcinogenesis in Rats by 12-O-Tetradecanoylphorbol-13-acetate¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830 [D. C. T.], and National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709 [P. N.]

Experiments were conducted to determine whether two-stage carcinogenesis could be observed in rat tracheal epithelium using 7,12-dimethylbenz(a)anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter. Heterotopic tracheal transplants in Fischer 344 rats were first exposed to 188 µg of DMBA delivered over a four-week period and subsequently to 100 µg of TPA. The TPA was released from beeswax pellets at a rate of 1.1 µg/day during the first two months and at a rate of 0.3 µg/day for the subsequent two months. TPA alone caused marked inflammation and epithelial hyperplasia in tracheal grafts but no metaplastic or dysplastic changes. The tumor incidence in tracheas exposed to DMBA only was 20%; that in tracheas exposed to DMBA followed by TPA was 72%. TPA also accelerated the appearance of tumors. The mean tumor induction time in the group exposed to DMBA only was 91 weeks as compared to 75 weeks in the group exposed to DMBA and TPA. The data indicate that TPA enhances the tracheal tumor response in a manner similar to that of tumor promotion in mouse skin.

¹ Research sponsored by the National Cancer Institute under Interagency Agreement Y01 CP 50200; the Office of Health and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation; and the National Institute of Environmental Health Sciences.

² Present address: Eastman Kodak Company, B-320 Toxicology Section, Health, Safety, and Human Factors Laboratory, Rochester, N. Y. 14650.

³ To whom requests for reprints should be addressed, at National Institute of Environmental Health Sciences, Post Office Box 12233, Research Triangle Park, N. C. 27709.

Received 4/ 3/80. Accepted 8/15/80.