INCREASED CELL-PROLIFERATION OF AZOXYMETHANE-INDUCED ABERRANT CRYPT FOCI OF RAT COLON

Aberrant crypt foci (ACF) were induced in the colon of F344 rats by s. c. injection of azoxymethane (AOM) twice in a three day-interval and e xamined after 4 and 12 weeks. The number and crypt multiplicity of ACF in each section of rat colon increased during this period. Histologic ally, aberrant crypts consisted of proliferating atypical epithelial c ells. Cell proliferation of ACF consisting of 4 aberrant crypts [ACF(4 )] and 2 aberrant crypts [ACF(2)], and normal crypts in the colon of r ats treated with AOM [normal crypts/AOM(+)] or saline [normal crypts/A OM(-)] was investigated by measurement of the mitotic index, prolifera ting cell nuclear antigen-labeling index (PCNA-EI), and 5-bromo-2'-deo xyuridine-labeling index (BrdU-LI). All three parameters of the cell p roliferative activity of ACF(4) were higher than those of normal crypt s/AOM(+) and normal crypts/AOM(-). The PCNA-LI and BrdU-LI in ACF(2) w ere the same as those in ACF(4). These findings suggest that ACF have increased cell proliferative activity. The correlation of these three parameters confirmed that the PCNA-LI is also a useful parameter for e valuating cell proliferative activity in ACF. The presence of many cel ls stained by PCNA in the upper portion of ACF suggested that ACF have more G(1) phase cells, which readily respond to mitogenic stimulation , than G(0) phase cells, which are predominant in normal crypts.