A comparative study of the efficacy of four barbiturates as promoters of the development of gamma-glutamyltranspeptidase-positive foci in the liver of carcinogen treated rats.

The promoting action of four barbiturates, and their modulation of the promoting action of a choline-devoid (CD) diet was investigated by quantitating the gamma-glutamyltranspeptidase (GGT)-positive foci which developed in the liver of rats exposed to a single injection of diethylnitrosamine. Phenobarbital (PHB), pentobarbital (PTB) and amobarbital (AMB), exerted a promoting action, while barbituric acid (BA) had no effect. Addition of PHB or PTB to a CD diet resulted in a synergistic promoting action, but AMB had only an additive effect. Feeding a CD diet to rats caused a stimulation of liver DNA synthesis and of cell proliferation. These effects of the diet were markedly inhibited by addition of PHB or PTB, while addition of AMB resulted only in an inhibition of the enhanced proliferation of hepatocytes. No inhibitory effect was exerted by BA. The results indicate that the liver tumor promoting action of PHB and of barbiturates is dependent upon biological effects related to the presence of an alkyl group in their side chain. It is hypothesized that the promoting action of the agents herein studied may involve two components, a stimulation of the proliferation of initiated liver cells, and a suppression of the proliferation of non-initiated cells.