SYNERGISTIC EFFECT OF A CHOLINE-DEVOID DIET AND PHENOBARBITAL IN PROMOTING THE EMERGENCE OF FOCI OF GAMMA-GLUTAMYLTRANSPEPTIDASE-POSITIVE HEPATOCYTES IN THE LIVER OF CARCINOGEN-TREATED RATS

Abstract

The effect of feeding phenobarbital (PHB) with a choline-devoid (CD) diet on the emergence of foci of .gamma.-glutamyltranspeptidase(GGT)-positive hepatocytes in the liver of carcinogen-treated rats was investigated. Male Sprague-Dawley rats were given a single dose of diethylnitrosamine (50 mg/kg) 18 h after a partial hepatectomy and 10 days later were placed on a plain choline-supplemented (CS) diet, a plain CD diet, or the CS and CD diets containing 0.06% PHB. Groups of rats were killed after 5 and 7 wk of feeding each of the 4 diets; the livers were taken, and the number and size of foci of GGT-positive hepatocytes were determined. In rats fed the CS + PHB diet, the number of foci per cm2 of liver section was greater than that in rats fed the plain CS diet but smaller than that in rats fed the plain CD diet. Addition of PHB to the CD diet resulted in twice as many foci as in the plain CD diet and foci larger than those resulting from the plain CD diet. The hepatocytes in the foci of rats fed the CD and CD + PHB diets showed, uniformly, not only GGT positivity but also a relative absence of fatty change. PHB and a CD diet, when combined, have a synergistic effect in promoting the evolution of liver cells, initiated by a chemical carcinogen, to foci of altered GGI-positive hepatocytes. This promoting regimen may become useful in studies concerned with the initiation and promotion stages of liver carcinogenesis.