ABERRANT CRYPT FOCI AND COLON TUMORS IN F344 RATS HAVE SIMILAR INCREASES IN PROLIFERATIVE ACTIVITY

Increased proliferative activity has been described frequently in the colons of animals treated with colon carcinogens and of patients at in creased risk of colon cancer; it has been proposed as an intermediate biomarker of colon cancer. Aberrant crypt foci, microscopic lesions id entified in whole-mount preparations of colons, are thought to be puta tive pre-neoplastic lesions. The present studies were carried out to e valuate the proliferative activity of aberrant crypt foci at several d ifferent time periods, and of tumors after a single dose of azoxymetha ne (AOM) in F344 rats. Rats were injected with 5-bromo-2'-deoxyuridine (BUdR) 1 hr before killing. Aberrant crypt foci and tumors were ident ified and marked in the whole-mount specimens, embedded in glycol meth acrylate, and evaluated for histochemically demonstrable hexosaminidas e activity. Hexosaminidase is known to be altered in over 95% of aberr ant crypt foci. Serial sections were evaluated for BUdR incorporation immunohistochemically with a monoclonal antibody. The mean proliferati ve activity of aberrant crypt foci in the distal colons was found to b e increased 3- to 4-fold over that of the adjacent normal crypts at ev ery time period analyzed (4 to 36 weeks) and was comparable to that se en in benign and malignant colon tumors in the same animals. The obser ved increase in proliferative activity further supports the hypothesis that aberrant crypt foci are putative pre-neoplastic lesions. Similar aberrant crypt foci, identified in human colons at increased risk of colon cancer, may provide important biomarkers for this common human c ancer. (C) 1994 Wiley-Liss, Inc.