Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity

B. Burchell, T. Ebner, S. Baird, Sahidan Senafi, D. Clarke, C. Brierley, L. Sutherland

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Five cloned human hepatic UDP-glucuronosyltransferase (UGT) cDNAs were stably expressed in tissue culture cell lines. More than 100 drugs and xenobiotics were used as substrates for glucuronidation catalyzed by the cloned human transferases to determine the chemical structures accepted as substrates. UGT-HP1 exhibited a limited substrate specificity for planar phenolic compounds, whereas UGT-HP4 was more accepting of nonplanar phenols, anthraquinones, flavones, alphatic alcohols, aromatic carboxylic acids, steroids and many drugs of varied structure. UGT-HP3 (bilirubin UGT) catalyzed the glucuronidation of ethinylestradiol. UGT-H6 and UGT-H25 (steroid bile acid UGTs) also catalyzed the glucuronidation of some xenobiotics. Levels of UGT-HP4 activity towards some substrates were sufficient to allow determination of kinetic parameters for the enzyme reaction. Further, metabolism of drugs could be studied by addition to the recombinant cell lines in culture and extraction of the media allowed analysis of glucuronide formation. The protection afforded against cytotoxic drugs was observed. The data presented here demonstrate the potential of using these recombinant cell lines for investigation of phase II metabolism by human UGTs and subtle differences in protein structure which affect their specificity.

Original languageEnglish
Pages (from-to)19-23
Number of pages5
JournalEnvironmental Health Perspectives
Volume102
Issue numberSUPPL. 9
Publication statusPublished - 1994
Externally publishedYes

Fingerprint

Glucuronosyltransferase
Glucuronides
Drug-Related Side Effects and Adverse Reactions
Liver
Toxicity
drug
toxicity
substrate
xenobiotics
steroid
Pharmaceutical Preparations
metabolism
bilirubin glucuronoside glucuronosyltransferase
Xenobiotics
Substrates
Metabolism
Cell Line
phenolic compound
carboxylic acid
phenol

Keywords

  • Bilirubin
  • Multigene family
  • Phenols
  • Stable expression
  • Steroids

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Public Health, Environmental and Occupational Health

Cite this

Burchell, B., Ebner, T., Baird, S., Senafi, S., Clarke, D., Brierley, C., & Sutherland, L. (1994). Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity. Environmental Health Perspectives, 102(SUPPL. 9), 19-23.

Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity. / Burchell, B.; Ebner, T.; Baird, S.; Senafi, Sahidan; Clarke, D.; Brierley, C.; Sutherland, L.

In: Environmental Health Perspectives, Vol. 102, No. SUPPL. 9, 1994, p. 19-23.

Research output: Contribution to journalArticle

Burchell, B, Ebner, T, Baird, S, Senafi, S, Clarke, D, Brierley, C & Sutherland, L 1994, 'Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity', Environmental Health Perspectives, vol. 102, no. SUPPL. 9, pp. 19-23.
Burchell, B. ; Ebner, T. ; Baird, S. ; Senafi, Sahidan ; Clarke, D. ; Brierley, C. ; Sutherland, L. / Use of cloned and expressed human liver UDP-glucuronosyltransferases for analysis of drug glucuronide formation and assessment of drug toxicity. In: Environmental Health Perspectives. 1994 ; Vol. 102, No. SUPPL. 9. pp. 19-23.
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