n-3 Polyunsaturated fatty acids alter benzo[a]pyrene metabolism and genotoxicity in human colon epithelial cell models
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
30572064
DOI
10.1016/j.fct.2018.12.021
PII: S0278-6915(18)30894-9
Knihovny.cz E-zdroje
- Klíčová slova
- Colon cancer, DNA damage, Docosahexaenoic acid, Eicosapentaenoic acid, Polycyclic aromatic hydrocarbon,
- MeSH
- adukty DNA metabolismus MeSH
- antikarcinogenní látky farmakologie MeSH
- benzopyren škodlivé účinky metabolismus MeSH
- epitelové buňky účinky léků MeSH
- histony metabolismus MeSH
- kontrolní body fáze S buněčného cyklu účinky léků MeSH
- kyselina eikosapentaenová farmakologie MeSH
- kyseliny dokosahexaenové farmakologie MeSH
- lidé MeSH
- mutageny škodlivé účinky metabolismus MeSH
- nádorové buněčné linie MeSH
- poškození DNA účinky léků MeSH
- rodina 1 cytochromu P450 metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adukty DNA MeSH
- antikarcinogenní látky MeSH
- benzopyren MeSH
- H2AX protein, human MeSH Prohlížeč
- histony MeSH
- kyselina eikosapentaenová MeSH
- kyseliny dokosahexaenové MeSH
- mutageny MeSH
- rodina 1 cytochromu P450 MeSH
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.
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