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Vol. 27, Issue 5, 569-573, May 1999
Institute of Toxicology, University of Tübingen, Germany
Human colon carcinoma Caco-2 cells were used to study the induction
of UDP glucuronosyltransferase (UGT) isoforms UGT1A6, UGT1A9, and
UGT2B7 by aryl hydrocarbon receptor agonists and by antioxidant-type inducers with
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and
t-butylhydroquinone (TBHQ), respectively. Early- (PF11) and late-passage clones (TC7) of Caco-2 cells, which show low and high
constitutive UGT1A6 expression, respectively, were selected. The
following results were obtained: 1) In Caco-2 cells UGT activity (4-methylumbelliferone as substrate) was significantly enhanced by 10 nM TCDD or 40 to 80 µM TBHQ and 2) duplex
reverse-transcription-polymerase chain reaction analysis showed
for the first time that the expression of human UGT1A6, UGT1A9, and
UGT2B7 was enhanced by 40 to 80 µM TBHQ; both UGT1A6 and UGT1A9 were
induced by 10 nM TCDD, whereas UGT2B7 was not induced by TCDD. The
results suggest that at least two human UGTs (UGT1A6 and UGT1A9) are
inducible by aryl hydrocarbon receptor agonists and even more isoforms
(UGT1A6, UGT1A9, and UGT2B7) are inducible by antioxidant-type inducers
in Caco-2 cells.
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