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Vol. 28, Issue 1, 34-37, January 2000
Institute of Chemistry Chemical Research Center, Hungarian Academy
of Sciences, Budapest, Hungary
Induction of UDP-glucuronosyltransferases (UGTs) toward thyroxine
(T4) and p-nitrophenol (pNP) by 3-methylcholanthrene (MC), dexamethasone (DEX), clofibrate (Cl), and MC combined with DEX or Cl
was studied in rat hepatocyte culture. We have developed a sensitive
method for the measurement of glucuronide conjugates of the two
substrates based on HPLC analysis of culture medium. MC, Cl, or DEX
increased the activity of T4 UGT. Combination of MC and Cl showed
additive effect, enzyme activity was enhanced compared with either MC
or Cl treatment alone (617, 441, and 217% of the control,
respectively). Combination of MC and DEX did not result in higher T4
UGT activity than MC treatment alone. Both MC and DEX enhanced the pNP
UGT activity (182 and 162% of the control, respectively). Combination
of MC with DEX resulted in additive effect. Cl treatment did not affect
pNP conjugation either alone or in combination with MC. Western blot
analysis revealed that only the amount of UGT1A1 was elevated by Cl and
DEX. In contrast, concentration of UGT1A6 was increased by MC.
Previous studies demonstrated that UGT1A1 inducers like
phenobarbital have no effect on T4 conjugation (Saito et al., 1991).
Our results suggest that Cl, a known inducer of UGT1A1, enhances the
activity of other enzyme(s) involved in T4 glucuronidation as well. It is well documented that DEX potentiates the inductory effect of polycyclic aromatic hydrocarbon on UGT1A6 (Xiao et al., 1995). In our
study, MC increased the rate of T4 glucuronidation, and DEX had no
additional effect on this reaction, suggesting that UGT1A6 is not the
only enzyme inducible by MC that can catalyze T4 conjugation.
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