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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F19%3AN0000155" target="_blank" >RIV/00027162:_____/19:N0000155 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/19:00502960 RIV/68378041:_____/19:00502960 RIV/00216224:14310/19:00113499

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0278691518308949?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0278691518308949?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.fct.2018.12.021" target="_blank" >10.1016/j.fct.2018.12.021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Food and Chemical Toxicology

ISSN

0278-6915

e-ISSN

1873-6351

Svazek periodika

124

Číslo periodika v rámci svazku

FEB 2019

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

11

Strana od-do

374-384

Kód UT WoS článku

000458712400031

EID výsledku v databázi Scopus

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