FISH-OIL BLOCKS AZOXYMETHANE-INDUCED RAT COLON TUMORIGENESIS BY INCREASING CELL-DIFFERENTIATION AND APOPTOSIS RATHER THAN DECREASING CELL-PROLIFERATION

The purpose of this study was to determine whether the protective effe ct of fish oil against colon carcinogenesis is due to decreased prolif eration, increased differentiation and/or increased apoptosis. Male Sp rague Dawley rats (n = 260) were fed one of two oils (corn or fish) an d two fibers (pectin or cellulose), plus or minus the carcinogen azoxy methane (AOM). Rats were killed at wk 18 (n = 80) or 36 (n = 180) for cytokinetic measurements. In vivo cell proliferation was measured by i ncorporation of bromodeoxyuridine into DNA, differentiation by binding of Dolichos biflorus agglutinin and apoptosis by immunoperoxidase det ection of digoxigenin labeled genomic DNA. Fish oil resulted in a lowe r adenocarcinoma incidence (56.1 vs. 70.3%) compared with corn oil. Th ere was no effect of fat or fiber on number of proliferative cells/cry pt column in either the proximal or distal colon. In contrast, fish oi l resulted in a greater degree of differentiation compared with corn o il in both colonic sites. In addition, fish oil resulted in a higher n umber of apoptotic cells/crypt column in both the proximal and distal colon as compared with corn oil. AOM treatment increased the ratio of proliferative cells/crypt column to apoptotic cells/crypt column in bo th the proximal and distal colon compared with saline controls. Fish o il, however, resulted in a lower ratio in both sites in the colon as c ompared with corn oil. These results suggest that an increase in apopt osis and differentiation, rather than a decrease in proliferation, acc ounts for the protective effect of fish oil against experimentally ind uced colon tumorigenesis.