DOWN-REGULATION OF EPIDERMAL GROWTH-FACTOR RECEPTORS IN RAT HEPATOCYTES TREATED WITH CLOFIBRIC ACID

The effect of clofibric acid (CA), a peroxisome proliferator and a non -genotoxic hepatocarcinogen was investigated on epidermal growth facto r (EGF) receptors in hepatocytes of female Sprague-Dawley rats treated at a dose of 9000 ppm in a diet for up to 13 weeks. Hepatocyte plasma membranes were isolated in Weeks 1 and 13, and assayed with [I-125]EG F. The binding of EGF to the hepatocyte plasma membranes was reduced i n Week 1 as a result of decreased number of low-affinity receptors. Th e fall of binding capacity was further evident in Week 13, which was a ssociated with decreased numbers of both high- and low-affinity recept ors. The equilibrium dissociation constant remained unchanged either i n Week 1 or 13. These results were in agreement with previous observat ions of a decreased hepatocyte response to mitogens after prolonged tr eatment with CA. This suggested that the CA-associated liver tumor pro moting effect is related to its ability to decrease the number of EGF receptors and the resultant aberrant growth environment. (C) 1997 Else vier Science Ireland Ltd.