Abstract
The promoting effect of phenobarbital (PB) on the tumor induction by naturally occurring carcinogens was investigated in this communication in inbred ACI rats.
In experiment A, the effect of PB on the development of neoplastic lesions by cycasin was investigated. Tumor development in the liver and the kidney was observed in groups of rats treated with a single oral administration of cycasin (100mg/kg body weight) and maintained on either a control diet or one supplemented with 0.05% PB. The feeding of PB 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 PB did not affect the incidence of kidney tumors in either sex. In addition, many large γ-glutamyl transpeptidase (GGT) -positive foci, which were thought to be preneoplastic lesions, developed in the liver of rats treated with cycasin and then PB, whereas a small number of tiny foci were seen in rats treated with cycasin alone. Long-term feeding of the 0.05% PB diet without treatment of cycasin induced many GGT-positive foci which, however, were small in size and observed only in periportal area of the liver. These data indicated that PB might possess a tumor promoting effect in terms of induction on neoplastic lesions in the liver. However, the effect was not observed in the kidney.
In experiment B, the effect of concomitant administration of PB on the carcinogenicity of Petasites japonicus MAXIM., a kind of coltsfoot containing a carcinogenic pyrrolizidine alkaloid, petasitenine, was examined. The hepatocarcinogenicity of petasites was found to be enhanced by concomitant administration of PB. This was substantiated by confirming the significant increase of the size of hemangioendothelial sarcoma of the liver, which is nonepithelial tumor, and a significant increase of lung metastases. However, PB did not influence the incidence or the size of epithelial tumor of the liver called neoplastic nodule.
