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Modulation of Epidermal Growth Factor Receptors in Rat Hepatocytes by Two Liver Tumor-promoting Regimens, a Choline-deficient and a Phenobarbital Diet¹

Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

The effect of two liver tumor-promoting regimens, a choline-deficient (CD) and a phenobarbital (.06% PB) diet, on the level of epidermal growth factor (EGF) receptor in rat hepatocytes was examined at 3, 10, and 28 days of feeding. Both diets produced a significant decrease in the number of cell surface receptors at 10 and 28 days of treatment. When PB was included in a CD diet, the decrease in the receptor number was evident even after 3 days feeding of the combined diet. Neither diet alone had any effect on the binding at that time. Along with the changes in the receptor number, the binding affinity of EGF to its receptor was also altered by these diets. Furthermore, PB and PB plus CD diets also decreased the EGF binding at the intracellular sites whereas CD diet showed no effects indicating that the decrease in surface binding of EGF by the promoter-treated hepatocytes was not due to rapid internalization of the receptors. The reduced level of hepatocyte surface EGF receptors represents the common property shared by two diverse types of the liver tumor promoters, and may thus be related to the tumor-promoting ability of these agents.

¹ Supported by grants from the National Institute of Health (CA 26556) and from the American Institute for Cancer Research.

² To whom requests for reprints should be addressed.

Received 4/30/87. Revised 10/14/87. Accepted 12/ 4/87.

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