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Development and Fate of Focal Epithelial Lesions in Tracheal Mucosa following Exposure to 7,12-Dimethylbenz(a)anthracene¹

Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37830

Tracheal transplants were exposed to 7,12-dimethylbenz(a)anthracene delivered continuously over a 4-week period from intraluminal pellets. Groups of tracheas were collected from 2 to 12 months after cessation of carcinogen exposure, and the number and type of focal lesions were scored. These focal lesions had previously been shown to arise well after cessation of carcinogen exposure. The highest incidence of focal lesions (all types) was found at 4 months. Over the subsequent 8 months, the incidence of tracheas with lesions declined from 72 to 44%, and the average number of lesions per exposed trachea declined from 2.5 to 1.3. Metaplasias with no or minimal atypia were the most common, and the drop in overall lesion incidence between 4 and 12 months was due primarily to a decrease in the observed frequency of these types of lesions, a finding which indicates that they are reversible. Significant numbers of more advanced (dysplastic) lesions occurred only from 4 months on. The incidence of the "advanced" lesions did not decline between 4 and 12 months. Invasive carcinomas first occurred at 4 months with an incidence of 5%. This did not change significantly during the subsequent time intervals.

A tumor induction study with a total of 86 tracheas was carried out over a 28-month period. The same carcinogen exposure was used as in the serial sampling study. The cumulative incidence of invasive carcinomas was 9% (that of all carcinomas, including carcinoma in situ, was 15%), with the first carcinoma appearing at 10 months and a mean induction time of 14 months. The cumulative incidence of advanced lesions in this study was 10%, but none of the tracheas collected more than 2 years after exposure contained carcinomas or advanced lesions. The data from these two experiments clearly indicate that, in tracheal epithelium exposed to a low dose of 7,12-dimethylbenz(a)anthracene: (a) a large number of carcinogen-induced lesions occur well after the acute toxic effects of 7,12-dimethylbenz(a)anthracene have passed; (b) the morphologically more advanced lesions develop with latent periods of 4 or more months; (c) many of these advanced lesions appear to persist for long periods of time without progressing further, while some may evolve into invasive neoplasms; and (d) most of the metaplastic lesions with little or no atypia regress, and some of the advanced lesions also appear to ultimately regress.

¹ Research jointly sponsored by the National Cancer Institute under Interagency Agreement 40-5-63; the National Institute of Environmental Health Sciences; and the Office of Health and Environmental Research, United States Department of Energy, under Contract W-7405-eng-26 with the Union Carbide Corporation.

² Present address: National Cancer Institute, Bethesda, Md. 20205.

³ Present address: National Institute of Environmental Health Sciences, P. O. Box 12233, Research Triangle Park, N. C. 27709.

Received 6/ 4/79. Accepted 8/31/79.