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3 záznamů v Medvik

Abstrakt

Metabolism of polycyclic aromatic hydrocarabons plays a major role both in their genotoxicity and in their non-genotoxic effects

Vondráček, Jan, 1970-
Autor Autorita ORCID Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic
Hýžďalová, Martina
Autor Hýžďalová, Martina Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic Departmento f Chemistry and Toxicology, Veterinary Research Institute, Brno, Czech Republic
Pivnička, J
Autor Pivnička, J Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
Zapletal, Ondřej, 1936-
Autor Autorita Department of Cytokinetics, Institute of Biophysics of the Czech Academy of Sciences, Brno, Czech Republic Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
Neča, Jiří
Autor Autorita Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic
Machala, Miroslav
Autor Autorita ORCID Institute of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic

Interdisciplinary toxicology. 2018 ; 11 (1) : 69. (23rd Interdisciplinary Toxicological Conference TOXCON 2018, The High Tatras, Slovakia, Stará Lesná, June 20-22, 2018)

ISSN 1337-6853
Medvik
Zdroj

Publikační typ
abstrakt z konference MeSH

Článek

Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a]pyrene via its histone deacetylase activity in colon epithelial cell models

Archives of toxicology. 2017 ; 91 (5) : 2135-2150. [pub] 20161109

Arch Toxicol
ISSN 1432-0738
Medvik
Zdroj

Butyrate, a short-chain 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, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells. It also co-stimulated the 7-ethoxyresorufin-O-deethylase (EROD) activity induced by the 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical ligand of the aryl hydrocarbon receptor. Up-regulation 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 HT-29 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. NaBt-induced 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 cells.