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@article{1390856,
author = {Zapletal, Ondřej and Tylichová, Zuzana and Neča, Jiří and Kohoutek, Jiří and Machala, Miroslav and Milcova, A. and Pokorna, Michaela and Topinka, Jan and Moyer, M.P. and Hofmanová, Jiřina and Kozubík, Alois and Vondráček, Jan},
article_location = {HEIDELBERG},
article_number = {5},
doi = {http://dx.doi.org/10.1007/s00204-016-1887-4},
keywords = {CYP1A1; Butyrate; Polycyclic aromatic hydrocarbons; DNA adducts; Histone deacetylases; Colon epithelial cells},
language = {eng},
issn = {0340-5761},
journal = {ARCHIVES OF TOXICOLOGY},
title = {Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a] pyrene via its histone deacetylase activity in colon epithelial cell models},
volume = {91},
year = {2017}
}
TY - JOUR
ID - 1390856
AU - Zapletal, Ondřej - Tylichová, Zuzana - Neča, Jiří - Kohoutek, Jiří - Machala, Miroslav - Milcova, A. - Pokorna, Michaela - Topinka, Jan - Moyer, M.P. - Hofmanová, Jiřina - Kozubík, Alois - Vondráček, Jan
PY - 2017
TI - Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a] pyrene via its histone deacetylase activity in colon epithelial cell models
JF - ARCHIVES OF TOXICOLOGY
VL - 91
IS - 5
SP - 2135-2150
EP - 2135-2150
PB - SPRINGER HEIDELBERG
SN - 03405761
KW - CYP1A1
KW - Butyrate
KW - Polycyclic aromatic hydrocarbons
KW - DNA adducts
KW - Histone deacetylases
KW - Colon epithelial cells
N2 - 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 II3 (at Lys14) and histone II4 (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.
ER -
ZAPLETAL, Ondřej, Zuzana TYLICHOVÁ, Jiří NEČA, Jiří KOHOUTEK, Miroslav MACHALA, A. MILCOVA, Michaela POKORNA, Jan TOPINKA, M.P. MOYER, Jiřina HOFMANOVÁ, Alois KOZUBÍK a Jan VONDRÁČEK. Butyrate alters expression of cytochrome P450 1A1 and metabolism of benzo[a] pyrene via its histone deacetylase activity in colon epithelial cell models. \textit{ARCHIVES OF TOXICOLOGY}. HEIDELBERG: SPRINGER HEIDELBERG, 2017, roč.~91, č.~5, s.~2135-2150. ISSN~0340-5761. Dostupné z: https://dx.doi.org/10.1007/s00204-016-1887-4.
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