Aberrant Crypts: Potential Preneoplastic Lesions in the Murine Colon

Abstract

Murine colons treated with the colon carcinogen azoxymethane (AOM) have been reported to contain aberrant crypts (AC), which are characterized by their larger size and wider pericryptal zones. The methodology used to visualize AC consists of staining the fixed, unsectioned colonic mucosa with methylene blue and transillumination of the luminal surface at a magnification of 40×. The objective of the present studies was to determine if AC demonstrate characteristics to support our hypothesis that they are putative preneoplastic lesions. Studies were designed to determine the time of occurrence of AC (Study I), the induction of AC in response to varying dosages of AOM ranging from 0.0 to 10.0 mg/kg body weight (Study II), and the effect of a high fat diet (20% fat by weight) on the number and size of AC (Study III). In all studies 4–6-week-old female CF₁ mice were used. In addition C57BL/6J female mice were used in Study I. The major findings were as follows: (a) the time period required to form AC was approximately 2 weeks following a single AOM injection (5 mg/kg); (b) a dose-dependent increase in the induction of AC was noted in response to AOM from none in the control group to a plateau level of 2.90 ± 0.38 foci at a dose of 5.0 mg/kg; (c) in comparison to the low fat group, the high fat group had a greater (P < 0.05) mean number of foci of AC per 5 cm of colon (15.67 ± 1.32 vs. 11.44 ± 1.44) and a larger (P < 0.05) mean size of foci of AC (0.0296 ± 0.0012 mm vs. 0.0249 ± 0.0012 mm) after 16 weeks on the respective diets; and (d) preliminary histological appearance of foci of AC revealed mild atypia to unequivocal dysplasia. The findings of the present study are consistent with the hypothesis that AC are putative preneoplastic lesions.