Journal Title
Title of Journal: Arch Toxicol
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Abbravation: Archives of Toxicology
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Publisher
Springer Berlin Heidelberg
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Authors: Ondřej Zapletal Zuzana Tylichová Jiří Neča Jiří Kohoutek Miroslav Machala Alena Milcová Michaela Pokorná Jan Topinka Mary Pat Moyer Jiřina Hofmanová Alois Kozubík Jan Vondráček
Publish Date: 2016/11/09
Volume: 91, Issue: 5, Pages: 2135-2150
Abstract
Butyrate a shortchain fatty acid produced by fermentation of dietary fiber is an important regulator of colonic epithelium homeostasis In this study we investigated the impact of this histone deacetylase HDAC inhibitor on expression/activity of cytochrome P450 family 1 CYP1 and on metabolism of carcinogenic polycyclic aromatic hydrocarbon benzoapyrene BaP in colon epithelial cells Sodium butyrate NaBt strongly potentiated the BaPinduced expression of CYP1A1 in human colon carcinoma HCT116 cells It also costimulated the 7ethoxyresorufinOdeethylase EROD activity induced by the 2378tetrachlorodibenzopdioxin a prototypical ligand of the aryl hydrocarbon receptor Upregulation of CYP1A1 expression/activity corresponded with an enhanced metabolism of BaP and formation of covalent DNA adducts NaBt significantly potentiated CYP1A1 induction and/or metabolic activation of BaP also in other human colon cell models colon adenoma AA/C1 cells colon carcinoma HT29 cells or in NCM460D cell line derived from normal colon mucosa Our results suggest that the effects of NaBt were due to its impact on histone acetylation because additional HDAC inhibitors trichostatin A and suberanilohydroxamic acid likewise increased both the induction of EROD activity and formation of covalent DNA adducts NaBtinduced acetylation of histone H3 at Lys14 and histone H4 at Lys16 two histone modifications modulated during activation of CYP1A1 transcription and it reduced binding of HDAC1 to the enhancer region of CYP1A1 gene This in vitro study suggests that butyrate through modulation of histone acetylation may potentiate induction of CYP1A1 expression which might in turn alter the metabolism of BaP within colon epithelial cellsThis study was supported by the Czech Science Foundation Project No 1309766S to AK the Czech Ministry of Agriculture RO 0515 to MM and Internal Grant Agency of the Ministry of Health of the Czech Republic NT145993/2013 to JK The authors acknowledge the assistance provided by the Research Infrastructure NanoEnviCz supported by the Ministry of Education Youth and Sports of the Czech Republic under Project No LM2015073 The authors wish to thank prof Chris Paraskeva School of Cellular and Molecular Medicine University of Bristol Bristol UK for kindly providing AA/C1 cell line The expert technical assistance of Radek Fedr Iva Lišková and Martina Urbánková is gratefully acknowledged
Keywords:
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