Enhancing Effect of Ethanol on Aflatoxin B(1)‐induced Hepatocarcinogenesis in Male ACI/N Rats

The modifying effect of ethanol (EtOH) on aflatoxin B(1) (AFB(1))‐induced hepatocarcinogenesis was examined in male ACI/N rats by chronic treatment at the post‐initiation phase. Rats received an ip injection of AFB(1) (1.5 mg/kg) twice a week for 10 weeks (a total of 20 doses). Following a week of acclimation, they were given 10% EtOH as drinking water for 56 weeks. The effect of EtOH on the hepatocarcinogenesis was evaluated in terms of the incidence of altered hepatocellular foci and neoplasms at the end of the experiment. Exposure to AFB(1) alone induced a substantial number of altered foci (6.98 iron‐excluding foci/cm(2)) in rats. The number of altered liver cell foci in rats receiving AFB(1) followed by EtOH was significantly increased (26.39 iron‐excluding foci/cm(2)). In the rats given EtOH after AFB(1) the total area and mean diameter of both iron‐excluding foci and altered foci identified in hematoxylin and eosin‐stained sections were significantly higher than in the rats exposed to AFB(1) alone. The incidence of liver cell tumors of the group given AFB, and EtOH (3/15, 20%) was higher than that of the group treated with AFB(1) alone (0/14, 0%). Treatment with EtOH alone for 56 weeks did not induce either. These results indicate an enhancing effect of EtOH on AFB(1)‐induced hepatocarcinogenesis when it is given in the promotion phase.