Effect of phenobarbital on the development of neoplastic lesions in the liver of cycasin-treated rats.

The effect of phenobarbital on the development of neoplastic lesions by cycasin was examined in inbred ACI rats. Tumor development in the liver and the kidney was observed in groups of rats treated with a single oral administration of cycasin (100 mg/kg body weight) and maintained on either a control diet or one supplemented with 0.05% phenobarbital. The feeding of phenobarbital diet after the application of cycasin significantly increased the incidence of liver tumors in female rats, but not in male rats. On the other hand, the administration of phenobarbital did not affect the incidence of kidney tumors in either sex. In addition, many large gamma-glutamyltranspeptidase (GGT)-positive foci, which were thought to be preneoplastic lesions, developed in the liver of rats treated with cycasin and then phenobarbital, whereas a small number of tiny foci were seen in rats treated with cycasin alone. Long-term feeding of the 0.05% phenobarbital diet without treatment of cycasin induced many GGT-positive foci which, however, were small-sized. These data indicated phenobarbital to possess a tumor-promoting effect in terms of induction of neoplastic lesions in the liver but not in the kidney.