Promotion-like enhancement of tracheal carcinogenesis in rats by 12-O-tetradecanoylphorbol-13-acetate

Abstract

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 microgram of DMBA delivered over a four-week period and subsequently to 100 microgram of TPA. The TPA was released from beeswax pellets at a rate of 1.1 microgram/day during the first two months and at a rate of 0.3 microgram/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.