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Histopathology Unit, Imperial Cancer Research Foundation, 35-43 Lincoln's Inn Fields, London WC2A 3PN, United Kingdom [E. A. M.]; Department of Pathology, University of Toronto and The North Western General Hospital, Toronto, Ontario, Canada M6M 3Z4 [A. M.]; and Departments of Foods and Nutrition, University of Manitoba, Winnipeg, Manitoba, Canada R3T 2N2 [R. P. B.]
The main objective of the present study was to sequentially analyze growth and morphological characteristics of aberrant crypt foci (ACF) in the rat colon. Sprague-Dawley rats were given a single injection of a carcinogenic dose of 1,2-dimethylhydrazine-HCl and at varying time points ranging from 2 to 57 weeks, groups of 5 rats were terminated. The number and crypt multiplicity of ACF were determined in the distal 8 cm of the colon. In addition, ACF were processed for histology and then graded for the presence of nuclear atypia using a score of 0–4. The findings of the present study demonstrated that ACF exhibit the characteristics expected for precursor lesions. ACF were present at all time intervals in large numbers in the colons of rats treated with 1,2-dimethylhydrazine-HCl and were present when adenocarcinomas were observed. The number of ACF with 4 or more crypts and those exhibiting a higher grade (grade 4) of nuclear atypia increased significantly at or beyond 19 weeks. These features of ACF, particularly the presence of nuclear atypia indicative of dysplasia, provide strong support for the hypothesis that ACF are precursor lesions of chemically induced colon cancer.
1 Supported in part by the Natural Sciences and Engineering Research Council, The Ludwig Foundation and National Cancer Institute of Canada. R. P. B. is a recipient of a Women in Science Career Award of the Natural Sciences and Engineering Research Council of Canada. Presented at the 80th Annual Meeting of the American Association for Cancer Research, San Francisco, California, May 25, 1989.
2 To whom requests for reprints should be addressed.
Received 11/ 7/90. Accepted 7/19/91.
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