Inhibitory effects of polyprenoic acid (E-5166) on N-2-fluorenylacetamide-initiated hepatocarcinogenesis in rats.

The effects of the newly synthesized polyprenoic acid, 3,7,11,15-tetramethyl-2,4,6,10,14-hexadecapentaenoic acid (E-5166) on N-2-fluorenylacetamide (FAA)-initiated hepatocarcinogenesis were examined in 6 groups of male ACI rats. The numbers of altered hepatocellular foci in rats of group 1 given a basal diet containing 0.02% FAA for 13 weeks and in rats of group 2 which received E-5166 by gavage (40 mg/kg, 3 times/week) at the same time as receiving the FAA diet were almost the same, indicating that E-5166 had no effect at the stage of carcinogen exposure. However, the number of foci in group 4, in which rats were given the basal diet and E-5166 after the termination of the carcinogen exposure, and were sacrificed 16 weeks later, was significantly smaller than that in group 3 maintained on the basal diet alone (P less than 0.05). The results suggests some anticarcinogenic activity of E-5166, possibly involving the phenotypic expression of the preneoplastic foci. Furthermore, the number of altered foci in rats of group 6 (given the liver-tumor promoter phenobarbital with E-5166 for 16 weeks after the administration of carcinogen) was also significantly smaller than that in rats of group 5, which received the promoter (P less than 0.05). The incidence of neoplastic nodules of the liver in group 6 at the end of the experiment was also lower than in group 5 (P less than 0.0014). These results suggest an antipromoting effect of the polyprenoic acid E-5166 on rat chemical hepatocarcinogenesis.