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

doi:10.1016/S0024-3205(97)00159-8

Life Sciences

Volume 60, Issue 22, 25 April 1997, Pages 1943-1951

https://doi.org/10.1016/S0024-3205(97)00159-8 Get rights and content

Abstract

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, β-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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^∗: Present Address: Laboratoire de Pharmacologie, URA CNRS 1288, Faculté de Médecine, Avenue de la Forêt de Haye, 54505 Vandoeuvre les Nancy, France.

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

Abstract

J. Biol. Chem.

Biochem. Pharmacol.

Arch. Biochem. Biophys.

Arch. Biochem. Biophys.

Biochem. Pharmacol.

Anal. Biochem.

Anal. Biochem.

Acta Pathol. Jpn.

Hepatology

Cell. Biol. Toxicol.

Drug Metab. Dispos.