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.

• 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

The aim of the present study was to evaluate in vitro effects of dietary phytochemicals naringenin, quercetin, and sesamin on the activities of ethoxy- (EROD; CYP1A) and benzyloxy- (BROD; CYP3A) resorufin O-dealkylases after the exposure to the cocktail of persistent organic pollutants (POPs). CD-1 mice were exposed from weaning, through gestation and lactation to a defined mixture of POPs. Hepatic microsomes were prepared from their female offspring at postnatal day 42. Hepatic EROD and BROD activity were evaluated in the presence of quercetin, naringenin, and sesamin at nine concentrations from 5 to 100000 nM. EROD activity was strongly inhibited by quercetin withKivalues from 1.7 to 2.6 μM. BROD activity was inhibited by quercetin withKivalues from 64.9 to 75.3 μM and naringenin withKivalues from 39.3 to 45.8 μM. The IC50andKivalues did not differ between the groups of mice with different levels of POPs exposure in any of the experimental sets. Sesamin did not inhibit either EROD or BROD. We concluded that the interactions of quercetin and naringenin with CYP1A and CYP3A in mice liver were not affected by the levels of POPs exposure.

• MeSH
• dioxoly farmakologie   MeSH
• flavanony farmakologie   MeSH
• jaterní mikrozomy enzymologie   patologie   MeSH
• látky znečišťující vzduch toxicita   MeSH
• lignany farmakologie   MeSH
• matka - expozice noxám škodlivé účinky   MeSH
• myši MeSH
• quercetin farmakologie   MeSH
• rodina 1 cytochromu P450 metabolismus   MeSH
• systém (enzymů) cytochromů P-450 metabolismus   MeSH
• těhotenství MeSH
• zpožděný efekt prenatální expozice chemicky indukované   enzymologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH