Induction of drug metabolizing enzymes in human liver cell line Hep G2.
Human cytochrome P-450, UDP-glucuronosyltransferase and sulphotransferase activities have been measured in the cell line Hep G2 following treatment of cells with 3-methylcholanthrene or phenobarbital. 3-Methylcholanthrene treatment caused a 20-30-fold increase in the O-deethylation of 7-ethoxycoumarin. The glucuronidation and sulphation of the product 7-hydroxycoumarin were increased 36 and 7 fold, respectively. In comparison, phenobarbital treatment did not increase these activities significantly. However, phenobarbital-inducible proteins were identified on "Western blots' using antibodies to a rat liver phenobarbital inducible P-450 form. The molecular masses of the proteins did not coincide with those expected for cytochromes P-450. However, characteristic of P-450 forms, the synthesis of these proteins was suppressed by 3-methylcholanthrene treatment. The Hep G2 cell line represents a potentially useful model for studying the regulation of human P-450 genes.
D002460:Cell Line; D003374:Coumarins / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008748:Methylcholanthrene / Q000494:pharmacology; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D013466:Sulfurtransferases / Q000378:metabolism
D003374:Coumarins; D007527:Isoenzymes; D004364:Pharmaceutical Preparations; C017299:7-ethoxycoumarin; D008748:Methylcholanthrene; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D013466:Sulfurtransferases; D010634:Phenobarbital