QUANTITATIVE EXPOSURE OF GRAFTED RAT TRACHEAS TO 7,12-DIMETHYLBENZ(A)ANTHRACENE

Abstract

A method was developed for continuously exposing tracheal epithelium to measured amounts of carcinogen. Beeswax was the vehicle for sustained release of carcinogen, and tracheas transplanted to s.c. sites were target tissues. In the experiment reported here, transplanted rat tracheas were exposed to a potent carcinogen, 7,12-dimethylbenz(a)anthracene (DMBA). The rate of release of DMBA from the beeswax carrier within the tracheal lumen approached 1st order when the initial concentration of carcinogen was high (3200-325 .mu.g in a 24.45 mg pellet). With lower concentrations, where the carcinogen was dissolved in the beeswax, initial release was rapid, and most of the carcinogen was delivered within 4 wk. At high DMBA dose levels, the entire tracheal epithelium was uniformly replaced by keratinizing squamous metaplasia after 1 wk of exposure, and after 2 mo., when from 280-910 .mu.g DMBA were delivered, all transplants developed invasive squamous carcinomas. Sarcomas also developed in 19% of the transplants. At lower dose levels the epithelial reactions were more varied, and tumor development was more protracted. The lowest DMBA dose presently known to induce carcinomas in this experimental model is 40 .mu.g, which is in the dose range used for tumor initiation in skin carcinogenesis studied in mice.