n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models

0502960 - BFÚ 2019 RIV GB eng J - Článek v odborném periodiku
Tylichová, Zuzana - Neca, J. - Topinka, Jan - Milcová, Alena - Hofmanová, Jiřina - Kozubík, Alois - Machala, M. - Vondráček, Jan
n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models.
Food and Chemical Toxicology. Roč. 124, FEB 2019 (2019), s. 374-384. ISSN 0278-6915. E-ISSN 1873-6351
Grant CEP: GA ČR GA13-09766S; GA ČR(CZ) GA16-17085S
Institucionální podpora: RVO:68081707 ; RVO:68378041
Klíčová slova: polycyclic aromatic-hydrocarbons * gene-expression * dna-adducts * h2ax phosphorylation
Obor OECD: Toxicology; Toxicology (UEM-P)
Impakt faktor: 4.679, rok: 2019
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S0278691518308949?via%3Dihub

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.
Trvalý link: http://hdl.handle.net/11104/0294801