Expression and inducibility of UDP-glucuronosyltransferases 1-naphthol in human cultured hepatocytes and hepatocarcinoma cell lines.
The UDP-glucuronosyltransferase (UGTs) isoforms involved in the conjugation of 1-naphthol were characterized in human cultured hepatocytes and in two human hepatocarcinoma cell lines, KYN-2 and Mz-Hep-1 in terms of expression, kinetics and induction by drugs. Their properties were compared to those of UGT1*6 stably expressed in the V79 cell line (V79UGT1*6), which glucuronidates 1-naphthol preferentially. The determination of kinetic constants for glucuronidation of 1-naphthol revealed a two-site model in human hepatocytes, but a one-site model in the two hepatocarcinoma cell lines. Southern blot analysis of RT-PCR products, showed that the UGT1*6 mRNA was expressed in KYN-2, but not in Mz-Hep-1 cells. However, a mRNA encoding a UGT different from UGT1*6 was expressed in Mz-Hep-1 cells. The two inducers, beta-naphthoflavone and rifampicin exerted a differential effect, depending on the cell lines considered. Altogether, the results suggest that, in hepatocytes, two UGT isoforms, which glucuronidate 1-naphthol are expressed and are differentialy regulated by inducers. Both KYN-2 and Mz-Hep-1 cells express one of the two different UGT isoforms found in hepatocytes. The UGT isoform present in KYN-2 cells corresponds to UGT1*6, whereas in Mz-Hep-1 cells the UGT isoform present was different from UGT1*6 and UGT1*7.
Abid
A
A
Centre du Médicament, URA CNRS 597, Nancy, France.
Sabolovic
N
N
Magdalou
J
J
D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000473:pathology; D002460:Cell Line; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology* / Q000473:pathology; D009284:Naphthols / Q000378:metabolism / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019324:beta-Naphthoflavone / Q000494:pharmacology
D005965:Glucuronates; D009284:Naphthols; C029350:1-naphthol; D019324:beta-Naphthoflavone; D014453:Glucuronosyltransferase; D012293:Rifampin