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Life Sci. 1997;60(22):1943-51.

Expression and inducibility of UDP-glucuronosyltransferases 1-naphthol in human cultured hepatocytes and hepatocarcinoma cell lines.

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Centre du M├ędicament, URA CNRS 597, Nancy, France.


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.

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