Elsevier

Toxicology

Volume 82, Issues 1–3, 5 October 1993, Pages 119-129
Toxicology

Drug and xenobiotic glucuronidation catalysed by cloned human liver UDP-Glucuronosyltransferases stably expressed in tissue culture cell lines

https://doi.org/10.1016/0300-483X(93)02607-IGet rights and content

Abstract

Two human UDP-Glucuronosyltransferase (UGT) cDNA clones were stably integrated into V79 chinese hamster fibroblast cells and the functional enzymes were expressed in this heterologous environment. More than 100 drugs and xenobiotics were used as substrates for glucuronidation, catalysed by the cloned UGTs to determine the chemical structures accepted as substrates. UGT HP1 exhibited a limited specificity for planar phenolic compounds, whereas UGT HP4 was more promiscuous in acceptance of non-planar phenols, anthraquinones, flavones, aliphatic alcohols, aromatic carboxylic acids, steroids and many drugs of varied structure. These conclusions are illustrated here by using a series of alkyl- and halophenols. This work indicates the considerable potential value in use of these recombinant cell lines to study human drug glucuronidation.

References (33)

  • R.H. Adamson et al.

    The fate of sulfadimethoxine in primates compared with other species

    Biochem. J.

    (1970)
  • B. Burchell et al.

    The UDP-glucuronosyltransferase gene superfamily. Suggested nomenclature based on evolutionary divergence

    DNA and Cell Biol.

    (1991)
  • N.K. Chaudhuri et al.

    Metabolism of tripelennamine in man

    Drug Metab. Dispos.

    (1976)
  • G.J. Dutton et al.

    Newer aspects of glucuronidation

    Prog. Drug. Metab.

    (1977)
  • L.J. Fischer et al.

    Formation and urinary excretion of cyproheptidine in monkeys, chimpanzees and humans

    Drug Metab. Dispos.

    (1980)
  • S. Fournel-Gigleux et al.

    Stable expression of two human liver glucuronosyltransferases in V79 cell cultures

    Mol. Pharmacol.

    (1991)
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