Abstract
Primary cultures of adult human hepatocytes were used to determine the capability of the human liver to respond to phenobarbital, 3-methylcholanthrene, troleandomycin and rifampicin, four compounds known to be potent inducers of hepatic cytochrome P-450 in various animal species. Both mRNA and corresponding protein of two major isoenzymes, that is, P-450 IIC8, 9, 10 and P-450 IIIA, were measured after daily exposure to the drugs for 3 days. Phenobarbital and rifampicin were found to increase the levels of P-450 IIC8, 9, 10 mRNA and protein while troleandomycin and 3-methylcholanthrene were ineffective. Different effects were obtained for P-450 IIIA. Both mRNA and related protein were markedly increased by troleandomycin and rifampicin and decreased by 3-methylcholanthrene. mRNAs were slightly increased by phenobarbital. The results demonstrate that human hepatocytes retain drug-inducible P-450 isoenzymes in primary culture and represent a unique approach to investigate regulation of human liver drug metabolizing enzymes.
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