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Quantitative Assessment of Generalized Epithelial Changes in Tracheal Mucosa following Exposure to 7,12-Dimethylbenz(a)anthracene¹

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

Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz(a)anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 µg 7,12-dimethylbenz(a)anthracene, respectively, were delivered. The first two types of exposures resulted only in generalized epithelial changes; these included hyperplasia and early metaplasia, both of which regressed rapidly, and persistent atrophic alterations. No focal epithelial lesions or tumors developed. The third type of exposure (160 µg 7,12-dimethylbenz(a)anthracene delivered in 4 weeks) resulted in the appearance of generalized mucosal changes with long-lasting, severe inhibition of mucus production. In addition, focal metaplastic lesions reappeared at 4 to 8 months after exposure, and invasive carcinomas developed after 1 year with an incidence of 9%. Overall carcinoma incidence, including carcinoma in situ, was 15%.

The studies emphasize the importance of the duration of carcinogen exposure, and they demonstrate the emergence of focal lesions when effective carcinogenic exposures are being used. The possible significance of epithelial atrophy in the pathogenesis of cancer in this experimental model is discussed.

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.

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