Dietary n-3 PUFA increases the apoptotic response to 1,2-dimethylhydrazine, reduces mitosis and suppresses the induction of carcinogenesis in the ratcolon

The effect of dietary fish oil on colonic crypt cell apoptosis and prolifer ation was examined in male Wistar rats, 24 and 48 h after administration of 1,2-dimethylhydrazine (DMH), and its influence on the induction of aberran t crypt foci (ACF) in the distal colon was assessed. Rats (125-150 g) fed a high-fat semi-synthetic diet containing corn oil (CO) were given DMH (30 m g/kg body wt) or a sham injection of EDTA/NaCl. Animals were then fed eithe r the CO diet or a diet in which fish oil (EPA 18.7%; DHA 8%) was substitut ed for corn oil. Subgroups of rats (n = 5) were killed after 24 and 48 h, a nd crypt cell apoptosis and proliferation were quantified by morphological criteria in isolated intact crypts from the mid and distal colon. Consumpti on of the fish oil diet (FO) was associated with increased apoptotic cell d eath (P < 0.001) and suppression of proliferation (P < 0.05) in colonic cry pts both 24 and 48 h after DMH, In a second experiment, animals were given three injections of DMH or sham injections of carrier at weekly intervals. For 48 h after each injection animals were fed either the CO or FO diet, bu t otherwise maintained on the CO throughout. The number and crypt multiplic ity of ACF in the distal colon were determined after 18 weeks, and animals given the FO diet for the 48 h period following carcinogen administration w ere found to have significantly fewer ACF than rats fed the CO diet (P < 0. 05). The data demonstrate that the fatty acid composition of the diet is an important determinant in the induction of carcinogenesis by DMH, The proli ferative and apoptotic response of the colonic crypt to carcinogen and fish oil, coupled with the reduced incidence of ACF, suggest n-3 PUFA can prote ct against the carcinogenic effects of DMH by mediating changes in the bala nce proliferation and cell death.