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@article{1642081,
author = {Tylichová, Zuzana and Neca, Jiri and Topinka, Jan and Milcova, Alena and Hofmanová, Jiřina and Kozubík, Alois and Machala, Miroslav and Vondráček, Jan},
article_location = {OXFORD},
article_number = {FEB 2019},
doi = {http://dx.doi.org/10.1016/j.fct.2018.12.021},
keywords = {Colon cancer; Eicosapentaenoic acid; Docosahexaenoic acid; Polycyclic aromatic hydrocarbon; DNA damage},
language = {eng},
issn = {0278-6915},
journal = {Food and Chemical Toxicology},
title = {n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models},
url = {https://www.sciencedirect.com/science/article/pii/S0278691518308949},
volume = {124},
year = {2019}
}
TY - JOUR
ID - 1642081
AU - Tylichová, Zuzana - Neca, Jiri - Topinka, Jan - Milcova, Alena - Hofmanová, Jiřina - Kozubík, Alois - Machala, Miroslav - Vondráček, Jan
PY - 2019
TI - n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models
JF - Food and Chemical Toxicology
VL - 124
IS - FEB 2019
SP - 374-384
EP - 374-384
PB - PERGAMON-ELSEVIER SCIENCE LTD
SN - 02786915
KW - Colon cancer
KW - Eicosapentaenoic acid
KW - Docosahexaenoic acid
KW - Polycyclic aromatic hydrocarbon
KW - DNA damage
UR - https://www.sciencedirect.com/science/article/pii/S0278691518308949
L2 - https://www.sciencedirect.com/science/article/pii/S0278691518308949
N2 - Dietary carcinogens, such as benzo[a]pyrene (BaP), are suspected to contribute to colorectal cancer development. n-3 Polyunsaturated fatty acids (PUFAs) decrease colorectal cancer risk in individuals consuming diets rich in PUFAs. Here, we investigated the impact of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid on metabolism and genotoxicity of BaP in human cell models derived from the colon: HT-29 and HCT-116 cell lines. Both PUFAs reduced levels of excreted BaP metabolites, in particular BaP-tetrols and hydroxylated BaP metabolites, as well as formation of DNA adducts in HT-29 and HCT-116 cells. However, EPA appeared to be a more potent inhibitor of formation of some intracellular BaP metabolites, including BaP-7,8-dihydrodiol. EPA also reduced phosphorylation of histone H2AX (Ser139) in HT-29 cells, which indicated that it may reduce further forms of DNA damage, including DNA double strand breaks. Both PUFAs inhibited induction of CYP1 activity in colon cells determined as 7-ethoxyresorufin-O-deethylase (EROD); this was at least partly linked with inhibition of induction of CYP1A1, 1A2 and 1B1 mRNAs. The downregulation and/or inhibition of CYP1 enzymes by PUFAs could thus alter metabolism and reduce genotoxicity of BaP in human colon cells, which might contribute to known chemopreventive effects of PUFAs in colon epithelium.
ER -
TYLICHOVÁ, Zuzana, Jiri NECA, Jan TOPINKA, Alena MILCOVA, Jiřina HOFMANOVÁ, Alois KOZUBÍK, Miroslav MACHALA a Jan VONDRÁČEK. n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models. \textit{Food and Chemical Toxicology}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, roč.~124, FEB 2019, s.~374-384. ISSN~0278-6915. doi:10.1016/j.fct.2018.12.021. 2019.
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