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The Regulation of ß-Hydroxy-ß-methylglutaryl Coenzyme A Reductase in Morris Hepatomas 5123C, 7800, and 9618A¹

McArdle Laboratory, Departments of Oncology and Pathology, The Medical School, University of Wisconsin, Madison, Wisconsin 53706

ß-Hydroxy-ß-methylglutaryl coenzyme A reductase was assayed in microsomes of host livers and hepatomas of rats fed a semisynthetic diet alone or with added cholestyramine or cholesterol under conditions of controlled feeding and lighting. Cholesterol feeding depressed the enzyme activity in all host livers but in none of the hepatomas. Cholestyramine feeding markedly increased ß-hydroxy-ß-methylglutaryl coenzyme A reductase activity in all host livers but had no effect on 5123C and 7800 hepatomas and caused only a slight elevation of enzyme activity in the 9618A hepatoma. A diurnal rise in enzyme activity, induced by feeding, was noted in the host livers and in two of the hepatomas but was absent in the slowest growing Morris hepatoma, 9618A. The persistence of diurnal rhythm and absence of regulation after cholesterol or cholestyramine feeding in hepatomas indicate that there are at least two different control mechanisms for this enzyme.

¹ This work was supported in part by National Cancer Institute Grant Ca-07175 and American Cancer Society Grant E-588G, as well as by Training Grant GM 5-T01-GM-00130-13 from the National Institute of General Medical Sciences.

² Recipient of Special Fellowship 1-F3-CA-44, 155-01 from the National Cancer Institute, during the tenure of which part of this work was carried out.

Received 1/25/71. Accepted 7/13/71.