- MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- monitorování životního prostředí MeSH
- mortalita MeSH
- nemoci dýchací soustavy epidemiologie MeSH
- novorozenec MeSH
- statistika jako téma MeSH
- vrozené vady MeSH
- výzkum MeSH
- znečištění ovzduší * analýza MeSH
- znečištění vzduchu ve vnitřním prostředí analýza MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
Epidemiologic studies indicate that prolonged exposure to particulate air pollution may be associated with increased risk of cardiovascular diseases and cancer in general population. These effects may be attributable to polycyclic aromatic hydrocarbons (PAHs) adsorbed to respirable air particles. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to PAH exposure. This study investigates relationships between exposure to PAHs, polymorphisms of these genes and DNA adducts in group of occupationally exposed policemen (EXP, N=53, males, aged 22-50 years) working outdoors in the downtown area of Prague and in matched "unexposed" controls (CON, N=52). Personal exposure to eight carcinogenic PAHs (c-PAHs) was evaluated by personal samplers during working shift prior to collection of biological samples. Bulky-aromatic DNA adducts were analyzed in lymphocytes by (32)P-postlabeling assay. Polymorphisms of metabolizing (GSTM1, GSTP1, GSTT1, EPHX1, CYP1A1-MspI) and DNA repair (XRCC1, XPD) genes were determined by PCR-based RFLP assays. As potential modifiers and/or cofounders, urinary cotinine levels were analyzed by radioimmunoassay, plasma levels of vitamins A, C, E and folates by HPLC, cholesterol and triglycerides using commercial kits. During the sampling period ambient particulate air pollution was as follows: PM10 32-55microg/m(3), PM2.5 27-38microg/m(3), c-PAHs 18-22ng/m(3); personal exposure to c-PAHs: 9.7ng/m(3) versus 5.8ng/m(3) (P<0.01) for EXP and CON groups, respectively. The total DNA adduct levels did not significantly differ between EXP and CON groups (0.92+/-0.28adducts/10(8) nucleotides versus 0.82+/-0.23adducts/10(8) nucleotides, P=0.065), whereas the level of the B[a]P-"like" adduct was significantly higher in exposed group (0.122+/-0.036adducts/10(8) nucleotides versus 0.099+/-0.035adducts/10(8) nucleotides, P=0.003). A significant difference in both the total (P<0.05) and the B[a]P-"like" DNA adducts (P<0.01) between smokers and nonsmokers within both groups was observed. A significant positive association between DNA adduct and cotinine levels (r=0.368, P<0.001) and negative association between DNA adduct and vitamin C levels (r=-0.290, P=0.004) was found. The results of multivariate regression analysis showed smoking, vitamin C, polymorphisms of XPD repair gene in exon 23 and GSTM1 gene as significant predictors for total DNA adduct levels. Exposure to ambient air pollution, smoking, and polymorphisms of XPD repair gene in exon 6 were significant predictors for B[a]P-"like" DNA adduct. To sum up, this study suggests that polymorphisms of DNA repair genes involved in nucleotide excision repair may modify aromatic DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from c-PAHs exposure.
- MeSH
- adukty DNA analýza MeSH
- dospělí MeSH
- financování organizované MeSH
- glutathiontransferasa genetika MeSH
- karcinogeny životního prostředí toxicita MeSH
- kyselina askorbová krev MeSH
- látky znečišťující vzduch toxicita MeSH
- lidé MeSH
- lipidy krev MeSH
- oprava DNA MeSH
- policie MeSH
- polycyklické aromatické uhlovodíky metabolismus toxicita MeSH
- polymorfismus genetický MeSH
- pracovní expozice MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
Acellular assay of calf thymus DNA+/-rat liver microsomal S9 fraction coupled with (32)P-postlabelling was used to study the genotoxic potential of organic compounds bound onto PM10 particles collected in three European cities-Prague (CZ), Kosice (SK) and Sofia (BG) during summer and winter periods. B[a]P alone induced DNA adduct levels ranging from 4.8 to 768 adducts/10(8) nucleotides in the concentration dependent manner. However, a mixture of 8 c-PAHs with equimolar doses of B[a]P induced 3.7-757 adducts/10(8) nucleotides, thus suggesting the inhibition of DNA adduct forming activity by interaction among various PAHs. Comparison of DNA adduct levels induced by various EOMs indicates higher variability among seasons than among localities. DNA adduct levels for Prague collection site varied from 19 to 166 adducts/10(8) nucleotides, for Kosice from 22 to 85 and for Sofia from 6 to 144 adducts/10(8) nucleotides. Bioactivation with S9 microsomal fraction caused 2- to 7-fold increase in DNA adduct levels compared to -S9 samples, suggesting a crucial role of indirectly acting genotoxic EOM components, such as PAHs. We have demonstrated for the first time a significant positive correlation between B[a]P content in EOMs and total DNA adduct levels detected in the EOM treated samples (R=0.83; p=0.04). These results suggest that B[a]P content in EOM is an important factor for the total genotoxic potential of EOM and/or B[a]P is a good indicator of the presence of other genotoxic compounds causing DNA adducts. Even stronger correlation between the content of genotoxic compounds in EOMs and total DNA adduct levels detected (R=0.94; p=0.005) was found when eight c-PAHs were taken into the consideration. Our findings support a hypothesis that a relatively limited number of EOM components is responsible for a major part of its genotoxicity detectable as DNA adducts by (32)P-postlabelling.
- MeSH
- finanční podpora výzkumu jako téma MeSH
- kuřecí embryo MeSH
- látky znečišťující vzduch terapeutické užití MeSH
- monitorování životního prostředí metody MeSH
- organické látky terapeutické užití MeSH
- testy genotoxicity MeSH
- velkoměsta MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- velkoměsta MeSH
- MeSH
- adukty DNA metabolismus škodlivé účinky MeSH
- arterioskleróza etiologie metabolismus patologie MeSH
- DNA metabolismus MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- svaly hladké cévní patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il., tab., grafy ; 32 cm
Stanovení DNA aduktů v hrudní aortě náhle zemřelých mužů ve věku 40 - 60 let, jako preklinického biomarkeru vývoje aterosklerotických změn.; Determination of DNA adducts in the thoracic aorta of sudden died men, aged 40 -60 years, as preclinical biomarkers of atherosclerotic changes.
- MeSH
- adukty DNA MeSH
- arterioskleróza genetika etiologie MeSH
- karcinogeny životního prostředí MeSH
- odběr biologického vzorku MeSH
- polymorfismus genetický MeSH
- vystavení vlivu životního prostředí MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- environmentální vědy
- angiologie
- biologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
