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-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.

Dietary Docosahexaenoic Acid Levels Influence the Outcome of Arabinosylcytosine Chemotherapy in L1210 Leukemic Mice

“…In a study of athymic nude mice, the growth rates of human breast tumors were reduced significantly in mice fed 4% linoleic acid compared with those fed 8% linoleic acid (18). Another report also showed a suppressive effect of a 5% safflower oil diet on hepatocarcinogenesis in rats (19). In addition to the abovementioned solid tumors, the present study further demonstrated that a low safflower oil diet containing 3.5% linoleic acid, although not as beneficial as DHA supplementation, prolonged the life span of the mice bearing L1210 leukemia, suggesting that a moderately low level of linoleic acid in the diet may also increase the chemosensitivity of the L1210 leukemic cells to AraC treatment.…”

Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases

“…Hu and Wang ( 2015 ) reported that the water extract of C. tinctorius has significant inhibitory effect on diethylnitrosamine-induced liver cirrhosis in rats. Besides, safflower oil, rich in n-6 polyunsaturated fatty acids, was reported to be able to alter the membrane fatty acid composition of the liver, and suppress the development of liver cell carcinoma induced by diethylnitrosamine in rats (Okuno et al, 1998 ). These results suggest that Ku-gong (safflower) may serve as a drug candidate for various liver diseases treatment.…”

The Antitumor Effects of α-Linolenic Acid

“…Cancer has been a constant threat to human life since its identification, and even when it is treatable, it greatly reduces quality of life. Many studies have shown that ALA exerts significant anticancer effects on multiple cancers [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. In Table 1 , we list a subset of ALA-sensitive cancers, including prostate cancer, BC, hepatocellular carcinoma, colorectal cancer (CRC), and pancreatic cancer.…”