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

Richard Wooster, Thomas Ebner, Lesley Sutherland, Douglas Clarke, Brian Burchell

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)119-129
Number of pages11
JournalToxicology
Volume82
Issue number1-3
DOIs
Publication statusPublished - 5 Oct 1993
Externally publishedYes

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