Suppression of EGF binding in rat liver by the hypolipidemic peroxisome proliferators, 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl)ac etamide and di(2-ethylhexyl)phthalate.
Dietary administration of 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl) acetamide(BR931) and di(2-ethylhexyl)phthalate (DEHP), hypolipidemic agents, to rats for 3-35 days induced a marked reduction in the hepatocyte surface and intracellular binding of [125I]EGF without affecting its binding affinity. The reduction was apparent after 3 days' feeding of BR931 and the magnitude of the reduction was consistently higher in hepatocytes of BR931-treated rats than those of DEHP-treated rats. The liver extracts and the sera from rats fed BR931 or DEHP for 4 weeks showed no inhibitory effects on the EGF binding of hepatocytes from rats fed a basal diet. Possible significance of the changes in relation to their hepatocarcinogenic action was discussed.
Gupta
C
C
Department of Pathology, University of Pittsburgh, School of Medicine, PA 15261.
Hattori
A
A
Shinozuka
H
H
D000818:Animals; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D010795:Phthalic Acids / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D000960:Hypolipidemic Agents; D010795:Phthalic Acids; D011743:Pyrimidines; D004815:Epidermal Growth Factor; C016908:pirinixil; D004051:Diethylhexyl Phthalate; D066246:ErbB Receptors