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The expression and inducibility of four CYP2C genes, including CYP2C8, -2C9, -2C18, and -2C19, was investigated in primary cultures of human hepatocytes. By the use of RNase protection assay and specific antibodies, each CYP2C mRNA and protein were quantified unequivocally. The four CYP2C mRNAs were expressed in human livers and cultured primary hepatocytes, but only the CYP2C18 protein was not detected.

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For the first time the experimental method of exogenous RNA has been used to evaluate the role of protein synthesis in different organs for the development of resistance to the soporific effect of barbiturates. Liver cytosolic RNA of phenobarbital-treated donors was found to reproduce completely the effect of phenobarbital-induced resistance to barbiturates in recipient rats: the reduction of hexenal-induced sleep and the increase of cytochrome P450 content in hepatic microsomes. Brain and renal RNAs had no influence on recipients.

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Liver microsomes, isolated from rats which had been treated with phenobarbital in vivo, were found to exhibit increased activities of oxidative demethylation and TPNH-cytochrome c reductase and an increased amount of CO-binding pigment. Simultaneous administration of actinomycin D or puromycin abolished the phenobarbital-induced enzyme synthesis. Increased rate of P(i) (32) incorporation into microsomal phospholipid was the first sign of phenobarbital stimulation and appeared 3 hours after a single injection of this drug.

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