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

doi:10.1016/0300-483X(93)02607-I

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 journal › Article › peer-review

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 language	English
Pages (from-to)	119-129
Number of pages	11
Journal	Toxicology
Volume	82
Issue number	1-3
DOIs	https://doi.org/10.1016/0300-483X(93)02607-I
Publication status	Published - 5 Oct 1993
Externally published	Yes

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

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.",

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author = "Richard Wooster and Thomas Ebner and Lesley Sutherland and Douglas Clarke and Brian Burchell",

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T1 - Drug and xenobiotic glucuronidation catalysed by cloned human liver UDP-Glucuronosyltransferases stably expressed in tissue culture cell lines

AU - Wooster, Richard

AU - Ebner, Thomas

AU - Sutherland, Lesley

AU - Clarke, Douglas

AU - Burchell, Brian

PY - 1993/10/5

Y1 - 1993/10/5

N2 - 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.

AB - 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.

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KW - Halophenols

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ER -

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

Abstract

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