© 1991 Oxford University Press
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Does response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon
Histopathology Unit, Imperial Cancer Research Foundation 35-43 Lincoln;s Inn Fields, London WC2A 3PN, UK
1Department of Pathology, University of Toronto Toronto, Ontario, Canada M6M 3Z4 and The North Western General Hospital Toronto, Ontario, Canada M6M 3Z4
2University of Manitoba Winnipeg, Manitoba, Canada R3T 2N2
3To whom reprint requests should be sent
Foci of aberrant crypts (ACF) have been identified in the unsectioned methylene blue stained rodent colons and hypothesized to represent precursor lesions of colon cancer. In the present study, induction and growth characteristics of ACF were investigated in response to a single injection of varying dosages of 1,2-dimethylhydrazine-2HCl (DMH), a colon carcinogen. Female Sprague-Dawley rats were given a single injection of DMH (5–150 mg/kg). Two and 19 weeks after the injection, animals were killed and their distal 10 cm of colons were enumerated for the number and crypt multiplicity of ACF. Number of ACF increased with increasing dosages of DMH plateauing at 100 mg/kg. However, percentage of ACF exhibiting different crypt multiplicity (1 to >4) were similar among different dose groups. Aberrant crypts and normal crypts were enumerated for total number of cells and number and distribution of S-phase cells along the crypt height 19 weeks after DMH injection after autoradiography. The labeling index (LI) (percentage of S-phase cells) and LI along the crypt height were determined. Compared to the surrounding normal crypts, aberrant crypts exhibited significantly higher (P < 0.05) number of cells (1122 ± 81 versus 411 ± 28) and higher (P < 0.05) LI (21 ± 1 versus 12 ± 1). For the eight ACF analysed in the present study, the distribution of S-phase cells in the aberrant crypts were similar to that of normal crypts in that S-phase cells were restricted to the lower two-thirds of the crypts rather than distributed throughout the height of the crypts as reported for adenomatous epithelium.
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