Abnormal Dietary Regulation of Glutamine Synthetase in Morris Hepatomas

Abstract

The series of Morris hepatomas offer unique opportunities to investigate the regulation of the cancer cell and how this regulation differs from that found in normal liver. One area of special interest concerns the failure of certain anabolic enzymes in hepatomas to change specific activity in response to dietary changes of the host animal in a manner similar to the enzyme in normal or host liver. Siperstein et al. (1, 2) showed that the biosynthesis of cholesterol was not suppressed in hepatomas from rats fed a cholesterol rich diet whereas a sharp reduction in cholesterol biosynthesis occurred in the liver of identically fed, tumor-free rats. Subsequently, Brown, Goldstein, and Siperstein (3) demonstrated that the synthesis of the rate limiting enzyme in cholesterol biosynthesis, β-hydroxy β-methylglutaryl coenzyme A reductase(HMG CoA reductase), was decreased in host liver when rats were subjected to the cholesterol rich diet; the synthesis of the enzyme in hepatomas did not change in response to an identical feeding schedule given to the host rat.