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

Abstract

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‐trans‐ferase‐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 phos‐pholipid fraction of the liver were found in Groups 3 and 4, respectively, than in the other groups. In contrast, a significant (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.