EGF Receptors of Hepatocytes from Rats Treated with Phenobarbital Are Sensitized to Down-Regulation by Phenobarbital in Culture

Hepatocytes from Fisher 344 rats treated with the liver tumor promoter phenobarbital (PhB; 0.1% in the drinking water, 2–3 months) exhibit reduced epidermal growth factor (EGF) binding and EGF-induced mitogenesis in culture. Similar responses are induced by >1 mM PhB added to the culture medium o...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2000-06, Vol.165 (2), p.115-126
Main Authors: Dalton, Shana R., Jirtle, Randy L., Meyer, Sharon A.
Format: Article
Language:English
Subjects:
Animals
Aryl Hydrocarbon Hydroxylases
Barbiturates - pharmacology
Biological and medical sciences
Blotting, Northern
Blotting, Western
Carcinogenesis, carcinogens and anticarcinogens
Carcinogens - pharmacology
Cells, Cultured
Chemical agents
CYP2B1/2
Cytochrome P-450 CYP2B1 - biosynthesis
Cytochrome P-450 Enzyme System - biosynthesis
Down-Regulation - drug effects
Enzyme Induction - drug effects
Epidermal growth factor receptor
Female
Liver - cytology
Liver - drug effects
Liver - metabolism
Liver Neoplasms, Experimental - chemically induced
Liver Neoplasms, Experimental - pathology
Male
Medical sciences
phenobarbital
Phenobarbital - blood
Phenobarbital - pharmacology
Rats
Rats, Inbred F344
Receptor, Epidermal Growth Factor - drug effects
Receptor, Epidermal Growth Factor - metabolism
RNA - biosynthesis
RNA - isolation & purification
Sodium-Potassium-Exchanging ATPase - metabolism
Steroid Hydroxylases - biosynthesis
tumor promotion
Tumors
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Summary:Hepatocytes from Fisher 344 rats treated with the liver tumor promoter phenobarbital (PhB; 0.1% in the drinking water, 2–3 months) exhibit reduced epidermal growth factor (EGF) binding and EGF-induced mitogenesis in culture. Similar responses are induced by >1 mM PhB added to the culture medium of hepatocytes from untreated rats. In this study, we demonstrated that hepatocyte EGFr protein, as determined by immunoblotting, was unchanged by treatment of rats with PhB. However, hepatocytes from PhB-treated rats are more sensitive to PhB in culture in that decreased EGF binding occurred with 0.05 mM PhB, a concentration also attained in plasma of rats exposed to PhB. Sensitization was reversible, as is tumor promotion, since hepatocytes from rats withdrawn from PhB for 1 month were unresponsive to
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.2000.8935