Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells. It also co-stimulated the 7-ethoxyresorufin-O-deethylase (EROD) activity induced by the 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical ligand of the aryl hydrocarbon receptor. Up-regulation of CYP1A1 expression/activity corresponded with an enhanced metabolism of BaP and formation of covalent DNA adducts. NaBt significantly potentiated CYP1A1 induction and/or metabolic activation of BaP also in other human colon cell models, colon adenoma AA/C1 cells, colon carcinoma HT-29 cells, or in NCM460D cell line derived from normal colon mucosa. Our results suggest that the effects of NaBt were due to its impact on histone acetylation, because additional HDAC inhibitors (trichostatin A and suberanilohydroxamic acid) likewise increased both the induction of EROD activity and formation of covalent DNA adducts. NaBt-induced acetylation of histone H3 (at Lys14) and histone H4 (at Lys16), two histone modifications modulated during activation of CYP1A1 transcription, and it reduced binding of HDAC1 to the enhancer region of CYP1A1 gene. This in vitro study suggests that butyrate, through modulation of histone acetylation, may potentiate induction of CYP1A1 expression, which might in turn alter the metabolism of BaP within colon epithelial cells.
- MeSH
- adukty DNA účinky léků metabolismus MeSH
- benzopyren metabolismus farmakokinetika MeSH
- beta-katenin metabolismus MeSH
- buňky HT-29 MeSH
- cytochrom P-450 CYP1A1 genetika metabolismus MeSH
- HCT116 buňky MeSH
- histondeacetylasa 1 antagonisté a inhibitory metabolismus MeSH
- histony metabolismus MeSH
- inhibitory histondeacetylas farmakologie MeSH
- kolon účinky léků metabolismus MeSH
- kyselina máselná farmakologie MeSH
- lidé MeSH
- metabolická inaktivace MeSH
- zesilovače transkripce účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The Northern Moravia Region is the most polluted region in the Czech Republic by particulate matter (PM2.5) and carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) as benzo[a]pyrene (B[a]P) by heavy industry and local heating. This specific situation was used to study the impact of air pollution on newborns in the exposed Karviná district and control district of České Budějovice. Biological material from newborns and mothers was collected in summer and winter seasons. This project is highly detailed, analyzing the concentrations of PAHs in ambient air and diet, in human breast milk, in the urine of mothers and newborns, using biomarkers of genetic damage as DNA adducts and gene expression analysis, biomarkers of oxidative stress as 8-oxodG adducts and lipid peroxidation (15-F2t-isoprostane immunoassay). All 400 children, for whom the biomarker data at delivery were obtained, will be followed for morbidity up to 2 years of age. The Northern Moravia Region seems to be to be a model area for studying the long-term impact of human health exposure to c-PAHs. Our observations will indicate possible genetic and oxidative damage in newborns, which may significantly affect their morbidity.
- MeSH
- adukty DNA MeSH
- benzopyren analýza MeSH
- deoxyguanosin analogy a deriváty analýza MeSH
- dieta MeSH
- dospělí MeSH
- genom * MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- látky znečišťující vzduch analýza MeSH
- lidé MeSH
- mateřské mléko chemie MeSH
- monitorování životního prostředí MeSH
- novorozenec MeSH
- oxidační stres MeSH
- pevné částice analýza MeSH
- polycyklické aromatické uhlovodíky analýza MeSH
- průmysl MeSH
- roční období MeSH
- těhotenství MeSH
- vystavení vlivu životního prostředí analýza MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
- Publikační typ
- abstrakt z konference MeSH
- Publikační typ
- abstrakt z konference MeSH
- Klíčová slova
- rostlinný olej, PAU, genotoxicita, DNA adukty, naftové emise, bionafta,
- MeSH
- adukty DNA analýza MeSH
- biopaliva analýza MeSH
- interakce genů a prostředí MeSH
- lidé MeSH
- oleje rostlin MeSH
- polycyklické aromatické uhlovodíky škodlivé účinky toxicita MeSH
- poškození DNA MeSH
- výfukové emise vozidel * analýza toxicita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
- MeSH
- benzopyren toxicita MeSH
- exprese genu MeSH
- financování organizované MeSH
- interpretace statistických dat MeSH
- látky znečišťující vzduch toxicita MeSH
- lidé MeSH
- mutační analýza DNA MeSH
- polycyklické aromatické uhlovodíky toxicita MeSH
- statistika jako téma MeSH
- testy genotoxicity MeSH
- výzkum MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Smoking in pregnancy increases a woman's risk of preterm delivery resulting in serious neonatal health problems and chronic lifelong disabilities for the children (e.g., mental retardation, learning problems). To study the effects of tobacco smoke on the placental transcriptome, we performed gene expression profiling on placentas from women exposed to tobacco smoke in pregnancy (N = 12) and from those without significant exposure (N = 64). Gene expression profiles were determined by Illumina HumanRef-8 v2 Expression BeadChips with 18,216 gene probes. Microarray data were normalized by quantile method and filtered for a detection P-value <0.01. Differential gene expression was determined by moderated t-statistic. A linear model was fitted for each gene given a series of arrays using lmFit function. Multiple testing correction was performed using the Benjamini and Hochberg method. Abundant levels of transcripts were found for genes encoding placental hormones (CSH1, CSHL1), pregnancy-specific proteins (PSG3, PSG4, PAPPA), and hemoglobins (HBB, HBG, HBA). Comparative analysis of smokers vs nonsmokers revealed the differential expression of 241 genes (P < 0.05). In smoker cohort, we detected high up-regulation of xenobiotic genes (CYP1A1, CYP1B1, CYB5A, COX412), collagen genes (e.g., COL6A3, COL1A1, COL1A2), coagulation genes (F5, F13A1) as well as thrombosis-related genes (CD36, ADAMTS9, GAS6). In smokers, we identified deregulated genes that show tissue non-specific induction and may be considered as general biomarkers of tobacco smoke exposure. Further, we also found genes specifically deregulated in the exposed placentas. Functional annotation analysis suggested processes and pathways affected by tobacco smoke exposure that may represent molecular mechanisms of smoke-induced placental abnormalities.
- MeSH
- dospělí MeSH
- kohortové studie MeSH
- kouření genetika metabolismus MeSH
- lidé MeSH
- messenger RNA biosyntéza genetika MeSH
- novorozenec MeSH
- placenta metabolismus fyziologie MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů metody MeSH
- stanovení celkové genové exprese metody MeSH
- těhotenství MeSH
- zpožděný efekt prenatální expozice genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- financování organizované MeSH
- interpretace statistických dat MeSH
- látky znečišťující vzduch analýza škodlivé účinky toxicita MeSH
- lidé MeSH
- polycyklické aromatické uhlovodíky analýza toxicita MeSH
- poškození DNA genetika MeSH
- velikost částic MeSH
- znečištění ovzduší analýza škodlivé účinky MeSH
- Check Tag
- lidé MeSH
