Effects of a Choline-deficient Diet and a Hypolipidemic Agent on Single GlutathioneS-Transferase Placental Form-positive Hepatocytes in Rat Liver

Abstract

Using the placental form of glutathione S-transferase (GST-P) as a marker of carcinogen-initiated hepatocytes, we investigated how a choline-deficient (CD) diet and BR931, a carcinogenic hypolipidemic agent, modify populations of single GST-P-positive hepatocytes. The liver of male Fischer rats (6-7 weeks old) fed a CS or basal diet contained mostly single or double GST-P-positive hepatocytes. Feeding a CD diet for 2-4 weeks led to increases in the number of aggregates of two and three GST-P-positive hepatocytes. By 8-12 weeks, there was an emergence of discrete foci of GST-P-positive hepatocytes consisting of more than 20 hepatocytes. Feeding a BR931 diet for 4-8 weeks resulted in no significant change in the number of single GST-P-positive hepatocytes in the liver as compared to feeding a basal diet. It is suggested that single GST-P-positive hepatocytes in the liver of relatively young rats maintained on a commercial diet may represent endogenously initiated cells. A CD diet promotes endogenously initiated cells to form larger aggregates or foci of GST-P-positive cells.