Suppression of EGF binding in rat liver by the hypolipidemic peroxisome proliferators, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-{beta}-hydroxyethyl)acetamide and di(2-ethylhexyl)phthalate

Dietary administration of 4-chloro-6-(2,3-xylidino)-2- pyrimidinylthio(N-ß-hydroxyethyl)acetamlde(BR931) and di(2-ethylhexyl)phthalate (DEHP), hypolipidemicagents, to rats for 3–35 days induced a marked reductionin the hepatocyte surface and intracellular binding of [¹²⁵I]EGFwithout affecting its binding affinity. The reduction was apparentafter 3 days' feeding of BR931 and the magnitude of the reductionwas consistently higher in hepatocytes of BR931-treated ratsthan those of DEHP-treated rats. The liver extracts and thesera from rats fed BR931 or DEHP for 4 weeks showed no inhibitoryeffects on the EGF binding of hepatocytes from rats fed a basaldiet. Possible significance of the changes in relation to theirhepatocarcinogenic action was discussed.