Modulation of Liver Microsomal Monooxygenase System by Dietary n-6/n-3 Ratios in Rat Hepatocarcinogenesis

Abstract

This study was designed to determine the effects of dietary n-3/n-6 fatty acid ratios on preneoplastic foci and the microsomal monooxygenase system in rat hepatocarcinogenesis. Male Sprague-Dawley rats were fed four kinds of diets containing 15% (wt/wt) fat with different n-6/n-3 ratios: low ratio (≥1.0) with tuna oil, low ratio (≥1.0) with perilla oil, moderate ratio (≤4.0), and high ratio (≤10.0). Hepatocarcinogenesis was induced by diethylnitrosamine and partial hepatectomy. The moderate ratio diet decreased significantly the area and number of placental glutathione S-transferase-positive foci compared with the high ratio diet and low ratio diet with perilla oil. The fatty acid composition of microsomal membrane varied extensively, reflecting the dietary n-6/n-3 ratios. Liver microsomal lipid peroxidation was significantly decreased in the group fed the low ratio diet with tuna oil compared with the moderate and high ratio groups. Glucose-6-phosphatase activity, which reflects membrane stability, was significantly higher in the low ratio groups than in the high ratio group. The monooxygenase activities were increased significantly in the moderate ratio group compared with the high ratio group. These results suggest that a moderate n-6/n-3 ratio (≤4.0) may be the most effective in decreasing preneoplastic foci by elevating the monooxygenase activities and n-3 fatty acids in fish oil may have a protective effect by lowering the lipid peroxidation and stabilizing the microsomal membrane during rat hepatocarcinogenesis.