Suppressive effect of low amounts of safflower and perilla oils on diethylnitrosamine-induced hepatocarcinogenesis in male F344 rats.

We have investigated the modulating effects of low amounts of dietary oils rich in polyunsaturated fatty acids (PUFA) on diethylnitrosamine (DEN)-induced hepatocarcinogenesis in male F344 rats. A total of 112 animals were divided into eight groups. Groups 1-4 were given drinking water containing 40 ppm DEN for five weeks. Groups 5-8 served as controls without DEN treatment. Groups 1 and 5 were fed a basal diet containing 5% beef tallow, Groups 2 and 6 were fed a 5% olive oil diet, Groups 3 and 7 were fed a 5% safflower oil diet, and Groups 4 and 8 were fed a 5% perilla oil diet for 21 weeks, starting 1 week before DEN exposure. Beef tallow, olive oil, safflower oil, and perilla oil are rich in saturated fatty acids, a monounsaturated fatty acid, n-6 PUFA, and n-3 PUFA, respectively. All rats were killed 20 weeks after the start of the experiment. Incidences of hepatocellular adenoma and carcinoma were 100% in DEN-treated groups, irrespective of dietary oils. Multiplicities of adenomas in Groups 3 and 4 were significantly (p < 0.05) lower than in Groups 1 and 2. Multiplicity of carcinoma in Group 3 was significantly (p < 0.05) lower than in Group 1. Mean volumes of placental glutathione S-transferase-positive foci per liver and the number of argyrophilic nucleolar organizer region proteins per nucleus in the liver tumors were significantly (p < 0.05) lower in Groups 3 and 4 than in Groups 1 and 2. ras mRNA expression in liver neoplasms was also suppressed significantly (p < 0.05) in Groups 3 and 4 compared with Groups 1 and 2. Significantly (p < 0.05) higher levels of n-6 and n-3 PUFA in the phospholipid fraction of the liver were found in Groups 3 and 4, respectively, than in the other groups. In contrast, a significantly (p < 0.05) decrease in monounsaturated fatty acid was observed in Groups 3 and 4 compared with Groups 1 and 2. These results suggest that safflower oil and perilla oil, rich in n-6 and n-3 PUFA, respectively, alter the membrane fatty acid composition of the liver and suppress the development of liver cell carcinoma in rats.