Differential induction of human liver UDP-glucuronosyltransferase activities by phenobarbital-type inducers

Biochem Pharmacol. 1987 Dec 1;36(23):4137-43. doi: 10.1016/0006-2952(87)90572-7.

Abstract

(1) UDP-glucuronosyltransferase (UDP-GT) activities and their inducibility were investigated in human liver microsomes from a "liver bank". (2) UDP-GT activities were differentially induced in liver microsomes from patients treated with the phenobarbital-type inducers phenytoin or pentobarbital. UDP-GT activity towards bilirubin was induced 3-fold. Enzyme activities towards paracetamol, benzo(a)pyrene-3,6-quinol, 4-methylumbelliferone and 1-naphthol were moderately induced and to similar extents (2-fold). In contrast, morphine and 4-hydroxybiphenyl glucuronidation were not significantly affected. Cytochrome P-450 dependent 7-ethoxycoumarin O-deethylase was increased 5-fold. (3) A human hepatoma cell line (Hep G2) was studied to obtain information on the inducibility of human UDP-GT activities by 3-methylcholanthrene-type inducers. UDP-GT activities towards benzo(a)pyrene-3,6-quinol and 1-naphthol were moderately but significantly induced by 3-methylcholanthrene-treatment of the cells (2-fold), whereas 7-ethoxyresorufin O-deethylase and 7-ethoxycoumarin O-deethylase were increased over 100- and 10-fold, respectively. (4) The results suggest the existence of differentially inducible UDP-GT isoenzymes in human liver. The findings may be useful as a guide to characterize human liver UDP-GT isoenzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / metabolism
  • Adolescent
  • Adult
  • Benzopyrenes / metabolism
  • Bilirubin / metabolism
  • Carcinoma, Hepatocellular / enzymology
  • Enzyme Induction / drug effects
  • Female
  • Glucuronosyltransferase / biosynthesis*
  • Humans
  • Hydroquinones / metabolism
  • Hymecromone / metabolism
  • Isoenzymes / biosynthesis*
  • Liver Neoplasms / enzymology
  • Male
  • Methylcholanthrene / pharmacology
  • Microsomes, Liver / enzymology*
  • Middle Aged
  • Naphthols / metabolism
  • Pentobarbital / pharmacology*
  • Phenytoin / pharmacology*
  • Tumor Cells, Cultured

Substances

  • Benzopyrenes
  • Hydroquinones
  • Isoenzymes
  • Naphthols
  • 1-naphthol
  • Acetaminophen
  • Hymecromone
  • Methylcholanthrene
  • Phenytoin
  • benzo(a)pyrene-3,6-quinol
  • Glucuronosyltransferase
  • Pentobarbital
  • Bilirubin