Modulating effects of diets high in omega-3 and omega-6 fatty acids in initiation and postinitiation stages of diethylnitrosamine-induced hepatocarcinogenesis in rats

The effects of sardine fish oil or corn oil on diethylnitrosamine (DEN)-ind uced hepatocarcinogenesis were investigated in male F334 rats, Starting at 5 weeks of age, animals mere divided into 11 groups and fed 23.5% corn oil (HCO) (groups 1 and 7) or 5% corn oil (LCO) (groups 1 and 8), 22.5% sardine oil + 1% corn oil (FO) semipurified diet (groups 3 and 9) or basal diet (C E-2) (groups 4-6, 10 and 11). At 6 weeks of age, all animals except the veh icle-treated groups were given DEN (200 mg/kg body weight, i.p. once meekly for 3 weeks). One week after the final exposure ;to DEN, groups 1-3 were c hanged to the basal diet, and groups 4-6 were snitched to the HCO, LCO or F O diet, respectively. Animals in groups 1-3 and 10 were given drinking wate r containing 0.05% phenobarbital (PB), Liver sections from the animals at t he termination of the experiment (24 weeks) were doubly stained for glutath ione S-transferase placental form (GST-P) and silver-stained nucleolar orga nizer regions (AgNORs). The multiplicity of hepatocellular neoplasms of gro up 1 was significantly larger than that of group 2 or 3, The number of GST- P-positive foci of group 2 or 3 was significantly smaller than that of grou p I. Among the groups fed the experimental diets in the postinitiation phas e (groups 4-6), no significant difference was found in the incidence of liv er tumors, AgNORs values of the enzyme-altered foci in rats of the HCO diet groups were larger than those of the other diet groups. These results indi cate that the enhancing effect of a high dose of corn oil in hepatocarcinog enesis is mainly present during the initiation phase but not during postini tiation phase, and fish oil rich in polyunsaturated omega-3 fatty acids cou ld inhibit DEN-induced hepatocarcinogenesis in rats.