Abstract
The effect of clofibric acid (CA), a peroxisome proliferator and a non-genotoxic hepatocarcinogen was investigated on epidermal growth factor (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 [ 125I]EGF. The binding of EGF to the hepatocyte plasma membranes was reduced in Week 1 as a result of decreased number of low-affinity receptors. The fall of binding capacity was further evident in Week 13, which was associated with decreased numbers of both highand low-affinity receptors. The equilibrium dissociation constant remained unchanged either in Week 1 or 13. These results were in agreement with previous observations of a decreased hepatocyte response to mitogens after prolonged treatment with CA. This suggested that the CA-associated liver tumor promoting effect is related to its ability to decrease the number of EGF receptors and the resultant aberrant growth environment.
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