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ToxSci Advance Access published online on February 23, 2005

Toxicological Sciences, doi:10.1093/toxsci/kfi130
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Toxicological Sciences © The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received October 31, 2004
Accepted February 8, 2005

Systems Toxicology

Inhibitory Effects of Vitamin A on TCDD-induced Cytochrome P-450 1A1 Enzyme Activity and Expression

Yan-Mei Yang 1, Dong-Yang Huang 1*, Ge-Fei Liu 1, Jiu-Chang Zhong 1, Kun Du 1, Yi-Fan Li 1, and Xu-Hong Song 1

1 Molecular Biology Center, Shantou University Medical College, Shantou, Guangdong 515041

* To whom correspondence should be addressed.
Dong-Yang Huang, E-mail: huangdy{at}stu.edu.cn


   Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an extremely potent environmental contaminant that produces a wide range of adverse biological effects, including the induction of cytochrome P450 1A1(CYP1A1) that may enhance the toxic effects of TCDD. Several studies indicated that concurrent supplementation of vitamin A could reduce the toxicity, and potentially inhibit CYP1A1 activity (measured as EROD activity). In the present study, we investigated the in vivo effects of vitamin A on EROD activities and the expression of CYP1A1 in the liver of TCDD-treated mice. In Experiment I, the mice were given a single oral dose of 40 µg TCDD/kg body weight with or without the continuous administration of 2500IU vitamin A/kg body weight/day, and were killed on day 1, 3, 7, 14 or 28. In Experiment II, the mice were given daily an oral dose of 0.1 µg TCDD/kg body weight with or without supplement of 2000IU vitamin A/kg body weight, and were killed on day 14, 28 or 42. In both experiments, TCDD caused liver damage and increase in relative liver weights, augmented the EROD activities and CYP1A1 expression, and increased the aryl hydrocarbon receptor (AhR) mRNA expression, but did not alter the AhR nuclear translocator (ARNT) mRNA expression. CYP1A1 mRNA expression and AhR mRNA expression showed a similar time course. The liver damage in TCDD+vitamin A-treated mice was less severe than that in TCDD-treated mice. EROD activities, CYP1A1 expression, and AhR mRNA expression in vitamin A + TCDD treated-mice were lower than those in TCDD-treated mice, indicating that supplementation of vitamin A might attenuate the liver damage caused by TCDD.

Keywords: vitamin A, 2,3,7,8-tetrachlorodibenzo-p-dioxin; CYP1A1; aryl hydrocarbon receptor; AhR nuclear translocator.
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