Effect of dietary eicosapentaenoic acid on azoxymethane-induced colon carcinogenesis in rats

The effects of eicosapentaenoic acid (EPA, n-3 polyunsaturated fatty acid) and linoleic acid (n-6 polyunsaturated fatty acid) on azoxymethane-induced colon carcinogenesis in rats were studied. Male Donryu rats were given two types of semipurified diet containing 4.7% EPA plus 0.3% linoleic acid and 5% linoleic acid. The rats were given s.c. injection of azoxymethane (7.4 mg/kg body weight once a week for 11 weeks) and sacrificed 15 weeks after the last injection of azoxymethane. The tumor incidence and tumor yields (tumors per rat) of the colon were significantly lower in rats on the EPA diet compared to those on the linoleic acid diet; i.e., 33%, 0.41 +/- 0.61 and 69%, 1.66 +/- 1.69, respectively. In the analysis of phospholipid fatty acid composition, the colon tumor showed higher levels of arachidonic acid and lower levels of linoleic acid than those in the normal colon mucosa in both diet groups. Despite the increase of arachidonic acid in colon tumor, the EPA diet suppressed the excessive production of prostaglandin E2, which may be accompanied with neoplastic formation, whereas linoleic acid diet caused a marked increase in the tumor content of prostaglandin E2 compared to normal colon mucosa. These results suggest that EPA exerts its inhibitory effect on colon carcinogenesis by modulating lipid metabolism and inhibiting prostaglandin E2 synthesis in tumor cells.