Increased susceptibility of adult rats to azoxymethane-induced aberrant crypt foci

The purpose of this study was to compare azoxymethane-induced aberrant cryp t foci development in the colons of young and adult rats. Young (4 weeks of age) and adult (50 weeks of age) Sprague-Dawley rats were treated with two weekly injections of azoxymethane or saline. Rats were kilted either 6 or 14 weeks following the first injection, and the number, size and location o f aberrant crypt foci were determined. At both the 6- and 14-week time poin ts, the number of aberrant crypt foci in older rats was significantly great er than in young rats (P < 0.01). A higher percentage of aberrant crypt foc i were found in the region from the mid-colon to the cecum in older rats as compared to young rats. Colonic cell proliferation was evaluated using bro modeoxyuridine immunohistochemistry. Colonic cell proliferation indices in the rectal, mid-colon and cecal regions of young and older rats were simila r in young compared to adult rats. Ten large ACF from each group were scree ned for mutations in the beta -catenin gene (Ctnnbl) by PCR single strand c onformation polymorphism. No mutations were detected. These results demonst rate that older female rats are more susceptible to the induction of aberra nt crypt foci by azoxymethane than young female rats. Differences in coloni c cell proliferation or beta -catenin mutations in these two age groups do not appear to be responsible for differences in aberrant crypt foci develop ment. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.