Abstract
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) andt-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.
Footnotes
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Send reprint requests to: Prof. Dr. Karl Walter Bock, Institute of Toxicology, University of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany
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This work was supported by the Deutsche Forschungsgemeinschaft (DFG).
- Abbreviations used are::
- AhR
- aryl hydrocarbon receptor
- BaP
- benzo(a)pyrene
- EROD
- ethoxyresorufinO-deethylase
- GAPDH
- glyceraldehyde phosphate dehydrogenase
- 4-MUF
- 4-methylumbelliferone
- NQO1
- NAD(P)H quinone oxidoreductase
- TBHQ
- t-butylhydroquinone
- TCDD
- 2,3,7,8-tetrachlorodibenzo-p-dioxin
- UGT
- UDP glucuronosyltransferase
- DMSO
- dimethyl sulfoxide
- RT-PCR
- reverse transcription-polymerase chain reaction, RT-PCR
- Received July 8, 1998.
- Accepted February 3, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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