The facilitated effect of retinol on rat hepatocarcinogenesis induced by 3'-methyl-4-dimethylaminoazobenzene.

To examine the influence of retinol acetate (retinol, known as an inhibitor of tumor promotion) on 3'-methyl-4-dimethyl-aminoazobenzene (3'MeDAB)-induced hepatocarcinogenesis, rats were fed with a diet containing 0.06% 3'MeDAB for 4 or 7 weeks and then with a normal diet for 21 or 18 weeks. Rats were given retinol (0, 6.25, 12.5 and 25.0 mg/rat, dissolved in DMSO) i.p. every 5 days from the 10th week to the 20th week. As a control, rats were fed a basal diet and given retinol at the same doses as mentioned above. At the 25th week, the incidence of hepatoma (hepatocellular carcinoma and cholangiocarcinoma) of each group was checked. In rats fed diet containing 3'MeDAB for 7 weeks, significant increases in the incidence of hepatoma were seen in retinol-treated groups at various doses. In rats fed 3'MeDAB diet for 4 weeks, all three doses also moderately, though not significantly, increased the incidence of hepatoma. No liver tumor was found in rats fed normal diet followed by treatment with retinol at any dose. Except for slight but detectable elevation of cellular retinoic acid binding protein levels in tumor tissues obtained from rats treated with retinol, no obvious differences in cellular retinol binding protein and gamma-glutamyl transpeptidase in the tumor tissues were observed between retinol-treated and untreated rats. Phytohemagglutinin-induced lymphocyte blastogenesis of the tumor-bearing rats with or without retinol treatment showed approximately 50% inhibition compared with that of rats fed normal diet without retinol treatment. These results indicated that the administration of retinol in the early stages of hepatocarcinogenesis enhanced the tumor induction, possibly due to the fixation of malignant transformation of the cells.