EXPRESSION AND INDUCIBILITY OF UDP-GLUCURONOSYLTRANSFERASES 1-NAPHTHOL IN HUMAN CULTURED-HEPATOCYTES AND HEPATOCARCINOMA CELL-LINES

The UDP-glucuronosyltransferase (UGTs) isoforms involved in the conjug ation of 1-naphthol were characterized in human cultured hepatocytes a nd in two human hepatocarcinoma cell lines, KYN-2 and Mz-Hep-1 in term s of expression, kinetics and induction by drugs. Their properties wer e compared to those of UGT16 stably expressed in the V79 cell line (V 79UGT16), which glucuronidates 1-naphthol preferentially. The determi nation of kinetic constants for glucuronidation of 1-naphthol revealed a two-site model in human hepatocytes, but a one-site model in the tw o hepatocarcinoma cell lines. Southern blot analysis of RT-PCR product s, showed that the UGT16 mRNA was expressed in KYN-2, but not in Mz-H ep-1 cells. However, a mRNA encoding a UGT different from UGT16 was e xpressed 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 dif ferentially regulated by inducers. Both KYN-2 and Mz-Hep-1 cells expre ss one of the two different UGT isoforms found in hepatocytes. The UGT isoform present in KYN-2 cells corresponds to UGT16, whereas in Mz-H ep-1 cells the UGT isoform present was different from UGT16 and UGT1* 7.