OBJECTIVES: This study aimed to assess the biological impact of occupational exposure to diesel exhaust (DE) including DE particles (DEP) from heavy-duty diesel-powered equipment in Norwegian tunnel finishing workers (TFW). METHODS: TFW (n=69) and referents (n=69) were investigated for bulky DNA adducts (by 32P-postlabelling) and expression of microRNAs (miRNAs) (by small RNA sequencing) in peripheral blood mononuclear cells (PBMC), as well as circulating free arachidonic acid (AA) and eicosanoid profiles in plasma (by liquid chromatography-tandem mass spectrometry). RESULTS: PBMC from TFW showed significantly higher levels of DNA adducts compared with referents. Levels of DNA adducts were also related to smoking habits. Seventeen miRNAs were significantly deregulated in TFW. Several of these miRNAs are related to carcinogenesis, apoptosis and antioxidant effects. Analysis of putative miRNA-gene targets revealed deregulation of pathways associated with cancer, alterations in lipid molecules, steroid biosynthesis and cell cycle. Plasma profiles showed higher levels of free AA and 15-hydroxyeicosatetraenoic acid, and lower levels of prostaglandin D2 and 9-hydroxyoctadecadienoic acid in TFW compared with referents. CONCLUSION: Occupational exposure to DE/DEP is associated with biological alterations in TFW potentially affecting lung homoeostasis, carcinogenesis, inflammation status and the cardiovascular system. Of particular importance is the finding that tunnel finishing work is associated with an increased level of DNA adducts formation in PBMC.

• Klíčová slova
• biomonitoring, diesel fumes, particulates, polyaromatic hydrocarbons (pahs), toxicology,
• MeSH
• adukty DNA krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• inhalační expozice analýza   MeSH
• látky znečišťující vzduch v pracovním prostředí analýza   MeSH
• leukocyty mononukleární chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lineární modely MeSH
• lipidy krev   MeSH
• mikro RNA krev   MeSH
• pracovní expozice škodlivé účinky   MeSH
• průřezové studie MeSH
• stavebnictví * MeSH
• výfukové emise vozidel toxicita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Norsko MeSH
• Názvy látek
• adukty DNA MeSH
• biologické markery MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• lipidy MeSH
• mikro RNA MeSH
• výfukové emise vozidel MeSH

Crude coal tar (CCT) contains polycyclic aromatic hydrocarbons (PAHs). Benzo[a]pyrene (BaP) is metabolized into a highly reactive metabolite benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) that is able to bind to DNA and creates BPDE-DNA adducts. Adducted DNA becomes immunogenic and induces immune response by production of antibodies against BPDE-DNA adducts (Ab-BPDE-DNA). Circulating Ab-BPDE-DNA was proposed as potential biomarker of genotoxic exposure to BaP (PAHs). Goeckerman therapy (GT) of psoriasis uses dermal application of CCT ointment (PAHs). In presented study (children with psoriasis treated by GT; n = 19) the therapy significantly increased the level of Ab-BPDE-DNA (EI = 0.29/0.19-0.34 vs. 0.31/0.25-0.40; median/lower-upper quartile; p < 0.01). The results support the idea of Ab-BPDE-DNA level as a possible tentative indicator of exposure, effects and susceptibility of the organism to the exposure of BaP (PAHs).

• Klíčová slova
• BPDE-DNA adducts, antibodies, children, coal tar, goeckerman therapy, polycyclic aromatic hydrocarbons, psoriasis,
• MeSH
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid analýza   MeSH
• adukty DNA krev   účinky léků   MeSH
• dehet uhelný škodlivé účinky   terapeutické užití   MeSH
• dítě MeSH
• keratolytika aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• poškození DNA účinky léků   MeSH
• předškolní dítě MeSH
• psoriáza farmakoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA MeSH
• dehet uhelný MeSH
• keratolytika MeSH

Some specific antibodies indicate the presence of antigenic structures on DNA (DNA adducts) that can play an important role in the process of mutagenesis and/or carcinogenesis. They indicate the presence of increased genotoxic potential (hazard) prior to the formation of disease (primary prevention). The present study was focused on the serum level of benzo[a]pyrene 7,8-diol-9,10-epoxide-DNA adducts antibodies (anti-BPDE-DNA) in psoriatic patients (n = 55) dermally exposed to different levels of polycyclic aromatic hydrocarbons (PAHs). The general goal of the study was to contribute to better understanding of the value of the assumed biomarker (anti-BPDE-DNA) for evaluation of the organism's answer to genotoxic exposure to PAHs. Elevated level of exposure to PAHs resulted in the increased level of anti-BPDE-DNA. However, almost all levels of anti-BPDE-DNA ranged within the field of low values. Both variants of GT (CCT-3% and CCT-5%) induced higher expression of anti-BPDE-DNA in the group of nonsmokers. Significant relations between the level of anti-BPDE-DNA and PASI score, total duration of the therapy, or time of UVR exposure were not found. Further studies are needed to reduce interpretation uncertainty of this promising bioindicator.

• MeSH
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA krev   imunologie   MeSH
• biologické markery krev   MeSH
• dehet uhelný terapeutické užití   MeSH
• dospělí MeSH
• kouření krev   MeSH
• kůže účinky léků   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• protilátky krev   MeSH
• psoriáza krev   imunologie   patologie   terapie   MeSH
• senioři MeSH
• terapie ultrafialovými paprsky MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA MeSH
• benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA MeSH Prohlížeč
• biologické markery MeSH
• dehet uhelný MeSH
• polycyklické aromatické uhlovodíky MeSH
• protilátky MeSH

The health of human populations living in industrial regions is negatively affected by exposure to environmental air pollutants. In this study, we investigated the impact of air pollution on a cohort of subjects living in Ostrava, a heavily polluted industrial region and compared it with a cohort of individuals from the relatively clean capital city of Prague. This study consisted of three sampling periods differing in the concentrations of major air pollutants (winter 2009, summer 2009 and winter 2010). During all sampling periods, the study subjects from Ostrava region were exposed to significantly higher concentrations of benzo[a]pyrene (B[a]P) and benzene than the subjects in Prague as measured by personal monitors. Pollution by B[a]P, particulate matter of aerodynamic diameter <2.5 µm (PM2.5) and benzene in the Ostrava region measured by stationary monitors was also higher than in Prague, with the exception of PM2.5 in summer 2009 when concentration of the pollutant was significantly elevated in Prague. To evaluate DNA damage in subjects from both locations we determined the levels of bulky DNA adducts in peripheral blood lymphocytes using the (32)P-postlabeling method. Despite higher B[a]P air pollution in the Ostrava region during all sampling periods, the levels of B[a]P-like DNA adducts per 10(8) nucleotides were significantly higher in the Ostrava subjects only in winter 2009 (mean ± SD: 0.21 ± 0.06 versus 0.28 ± 0.08 adducts/10(8) nucleotides, P < 0.001 for Prague and Ostrava subjects, respectively; P < 0.001). During the other two sampling periods, the levels of B[a]P-like DNA adducts were significantly higher in the Prague subjects (P < 0.001). Multivariate analyses conducted among subjects from Ostrava and Prague separately during all sampling periods revealed that exposure to B[a]P and PM2.5 significantly increased levels of B[a]P-like DNA adducts in the Ostrava subjects, but not in subjects from Prague.

• MeSH
• adukty DNA krev   MeSH
• benzopyren toxicita   MeSH
• biologické markery analýza   krev   MeSH
• dospělí MeSH
• látky znečišťující vzduch analýza   toxicita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• multivariační analýza MeSH
• pevné částice škodlivé účinky   analýza   MeSH
• polycyklické aromatické uhlovodíky analýza   toxicita   MeSH
• roční období MeSH
• velkoměsta MeSH
• vitaminy krev   MeSH
• znečištění ovzduší škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• velkoměsta MeSH
• Názvy látek
• adukty DNA MeSH
• benzopyren MeSH
• biologické markery MeSH
• látky znečišťující vzduch MeSH
• pevné částice MeSH
• polycyklické aromatické uhlovodíky MeSH
• vitaminy MeSH

(32)P-postlabelling and PAH-ELISA using the antiserum #29 were employed to analyze DNA adducts in venous and umbilical cord blood and the placenta of 79 mothers giving birth to 80 living babies in Prague (Czech Republic). Ambient air exposure was measured by stationary measurements of basic air pollutants (PM2.5, c-PAHs) during the entire pregnancy. Tobacco smoke exposure was assessed by questionnaire data and by plasma cotinine levels. The total DNA adduct levels in the lymphocytes of mothers and newborns were elevated by 30-40% (p<0.001) compared with the placenta. B[a]P-like DNA adduct (adduct with the identical chromatographic mobility on TLC as major BPDE derived DNA adduct) levels were elevated in the blood of mothers compared with the placenta and the blood of newborns (p<0.05 and p<0.01). In tobacco smoke-exposed mothers, higher DNA adduct levels in the blood of mothers and newborns compared with the placenta were found (p<0.001), whereas the total and B[a]P-like adduct levels were comparable in the blood of mothers and newborns. B[a]P-like adducts were elevated in the blood of mothers unexposed to tobacco smoke compared with that of corresponding newborns and the placenta (p<0.01). Total and B[a]P-like DNA adducts were increased in the placenta of tobacco smoke-exposed compared with unexposed mothers (p<0.001 and p<0.01). In lymphocytes of tobacco smoke-exposed mothers, the comparison of total adduct levels (1.18+/-0.67 vs. 0.92+/-0.28) and B[a]P-like DNA adducts (0.22+/-0.12 adducts/10(8) nucleotides vs. 0.15+/-0.06 adducts/10(8) nucleotides) with newborns indicated a 30-40% increase of adducts in mothers. Almost equal PAH-DNA adduct levels were detected by anti-BPDE-DNA ELISA in the placenta of tobacco smoke-exposed and -unexposed mothers. Our results suggest a protective effect of the placental barrier against the genotoxic effect of some tobacco smoke components between the circulation of mother and child. We found a correlation between adduct levels in the blood of mothers and newborns.

• MeSH
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid metabolismus   MeSH
• adukty DNA krev   metabolismus   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• ELISA MeSH
• fetální krev metabolismus   MeSH
• kotinin krev   MeSH
• kouření * MeSH
• látky znečišťující vzduch krev   MeSH
• lidé MeSH
• lymfocyty účinky léků   MeSH
• maternofetální výměna látek MeSH
• matka - expozice noxám * MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• placenta účinky léků   MeSH
• plod krevní zásobení   MeSH
• polycyklické aromatické uhlovodíky krev   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 7,8-dihydro-7,8-dihydroxybenzo(a)pyren 9,10-oxid MeSH
• adukty DNA MeSH
• benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA MeSH Prohlížeč
• biologické markery MeSH
• kotinin MeSH
• látky znečišťující vzduch MeSH
• polycyclic aromatic hydrocarbons-DNA adduct MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH

Oxidative damage to macromolecules may have numerous negative health consequences. We measured oxidative damage to DNA, proteins and lipids in 80 newborns and 79 mothers, analyzed the effect of mother's tobacco smoke exposure on oxidative stress, and assessed correlations between oxidative stress markers and bulky and PAH (polycyclic aromatic hydrocarbons)-specific DNA adducts. Mean levels (+/-S.D.) of 8-oxodeoxyguanosine (8-oxodG) per 10(5) dG in the placenta were 2.85+/-0.78; we did not see a difference between 8-oxodG levels in newborns born to mothers exposed and unexposed to tobacco smoke. Protein carbonyl levels, a marker of protein oxidation, were comparable in the umbilical cord and in maternal venous blood plasma (17.4+/-3.2 and 17.6+/-4.2nmol/ml plasma in newborns and mothers, respectively, p=0.66). Lipid peroxidation measured as levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) in plasma was significantly higher in newborns than in mothers (362+/-129 and 252+/-130pg/ml in newborns and mothers, respectively, p<0.001). We did not find any effect of tobacco smoke exposure on either biomarker in any group. Levels of both protein carbonyls and 15-F(2t)-IsoP in cord blood significantly correlated with those in maternal plasma (p<0.001). 8-oxodG levels positively correlated with plasma carbonyls in cord plasma, as well as with cotinine levels (marker of tobacco smoke exposure) in maternal plasma. 8-oxodG levels also correlated with bulky DNA adducts in lymphocyte DNA of newborns and mothers and with PAH-DNA adducts in the placenta. Our results showed higher lipid peroxidation in newborns than in mothers, close correlation of analyzed oxidative stress markers between newborns and mothers, and a relationship between oxidative stress and induction of DNA adducts.

• MeSH
• 8-hydroxy-2'-deoxyguanosin MeSH
• adukty DNA krev   MeSH
• biologické markery krev   MeSH
• deoxyguanosin analogy a deriváty   metabolismus   MeSH
• dospělí MeSH
• ELISA MeSH
• F2-isoprostany metabolismus   MeSH
• fetální krev chemie   MeSH
• karbonylace proteinů MeSH
• kotinin analýza   MeSH
• kouření * MeSH
• krevní proteiny analýza   MeSH
• látky znečišťující vzduch krev   MeSH
• lidé MeSH
• lymfocyty účinky léků   MeSH
• maternofetální výměna látek MeSH
• matka - expozice noxám * MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• oxidace-redukce MeSH
• oxidační stres * MeSH
• peroxidace lipidů MeSH
• placenta metabolismus   MeSH
• polycyklické aromatické uhlovodíky krev   MeSH
• těhotenství MeSH
• vitamin A analýza   MeSH
• vitamin E analýza   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 5-F(2t)-isoprostane MeSH Prohlížeč
• 8-hydroxy-2'-deoxyguanosin MeSH
• adukty DNA MeSH
• biologické markery MeSH
• deoxyguanosin MeSH
• F2-isoprostany MeSH
• kotinin MeSH
• krevní proteiny MeSH
• látky znečišťující vzduch MeSH
• polycyclic aromatic hydrocarbons-DNA adduct MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH
• vitamin A MeSH
• vitamin E MeSH

A study employing several biomarkers of styrene exposure and genotoxicity was carried out in a group of lamination (reinforced plastic) workers and controls, who had been repeatedly sampled during a 3-year period. Special attention will be paid to the last sampling (S.VI), reported here for the first time. Styrene concentration in the breathing zone, monitored by personal dosimeters, and urinary mandelic acid (MA) were measured as indicators of external exposure. Blood samples were assayed for styrene-specific O6-guanine adducts in DNA, N-terminal valine adducts of styrene in haemoglobin, DNA single-strand breaks (SSB), determined by use of the single cell gel electrophoresis (Comet) assay), and hypoxanthine guanine phosphoribosyl transferase (HPRT) mutant frequencies (MF) in T-lymphocytes. O6-styrene guanine adduct levels were significantly higher in the exposed group (5.9 +/- 4.9 adducts/10(8) dNp) as compared to laboratory controls (0.7 +/- 0.8 adducts/10(8) dNp; P = 0.001). DNA adduct levels significantly correlated with haemoglobin adducts, SSB parameters and years of employment. Styrene-induced N-terminal valine adducts were detected in the lamination workers (1.7 +/- 1.1 pmol/g globin), but not in the control group (detection limit 0.1 pmol/g globin). N-terminal valine adducts correlated strongly with external exposure indicators, DNA adducts and HPRT MF. No significant correlation was found with SSB parameters. A statistically significant difference in HPRT MF was observed between the laminators (22.3 +/- 10.6/10(6)) and laboratory controls (14.2 +/- 6.5/10(6), P = 0.039). HPRT MF in the laminators significantly correlated with styrene concentration in air, MA and haemoglobin adducts, as well as with years of employment and age of the employees. No significant difference (P = 0.450) in MF between the laminators and the factory controls was observed. Surprisingly, we detected differences in MF between sexes. When data from all measurements were combined, women showed higher MF (geometric mean 15.4 vs. 11.2 in men, P = 0.020). The styrene-exposed group exhibited significantly higher SSB parameters (tail moment (TM), tail length (TL) and the percentage of DNA in the tail (TP)) than the control group (P < 0.001). SSB parameters correlated with indicators of external exposure and with O6-styrene guanine adducts. No significant correlation was found between SSB parameters and haemoglobin adducts or HPRT MF. The data encompassing biomarkers from repeated measurements of the same population over a 3-year period are discussed with respect to the mechanisms of genotoxic effects of styrene and the interrelationship of individual biomarkers.

• MeSH
• adukty DNA krev   MeSH
• biologické markery analýza   MeSH
• dechové testy MeSH
• dospělí MeSH
• hemoglobiny účinky léků   MeSH
• hypoxanthinfosforibosyltransferasa genetika   MeSH
• jednovláknová DNA účinky léků   MeSH
• kometový test MeSH
• kyseliny mandlové moč   MeSH
• látky znečišťující vzduch v pracovním prostředí škodlivé účinky   analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• následné studie MeSH
• plastické hmoty MeSH
• poškození DNA * MeSH
• pracovní expozice škodlivé účinky   analýza   MeSH
• regresní analýza MeSH
• styren škodlivé účinky   analýza   chemie   MeSH
• T-lymfocyty účinky léků   enzymologie   MeSH
• valin analogy a deriváty   analýza   účinky léků   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• biologické markery MeSH
• hemoglobiny MeSH
• hypoxanthinfosforibosyltransferasa MeSH
• jednovláknová DNA MeSH
• kyseliny mandlové MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• mandelic acid MeSH Prohlížeč
• plastické hmoty MeSH
• styren MeSH
• valin MeSH

The DNA adduct levels in total white blood cells (WBC) and lymphocytes (LYM) isolated from the blood of the same individuals were evaluated using the 32P-postlabelling assay for bulky aromatic adducts. In this study, 68 male coke oven workers and 56 machines workers as a matched control were enrolled. Personal monitors were used to evaluate exposure to eight carcinogenic PAHs, including B[alpha]P, during an 8-h working shift. The exposure among coke even workers ranged widely from 0.6 to 547 micrograms/m3 and from 2 to 62,107 ng/m3, for carcinogenic PAHs and B[alpha]P, respectively. The respective values in controls were from 0.07-1.64 microgram/m3 and from 1-63 ng/m3. A significant correlation between WBC- and LYM-DNA adduct levels was found (r = 0.591, P < 0.001). DNA adduct levels in both WBC and LYM were significantly elevated in coke oven workers as compared with controls, but adduct levels were generally low (WBC: medians 2.61 vs. 1.83 LYM: 2.47 vs. 1.65 adducts/10(8) nucleotides). LYM-DNA adduct levels were significantly higher for smokers as compared with nonsmokers in both the exposed and control groups. No such differences in WBC-DNA adduct levels were observed. Positive significant correlations were found at the individual level between DNA adducts in both cell types and carcinogenic PAHs and/or B[alpha]P in the inhaled air (r = 0.38-0.45, P < 0.001). A significant correlation at the individual level between LYM-DNA adducts and urinary cotinine was also observed (r = 0.37, P < 0.001). No differences in DNA adduct levels could be attributed to GSTM1 or NAT2 genotype in either group. Nor was there any clear association of DNA adduct levels with combined GSTM1/NAT2 genotypes. The effect of personal exposure to carcinogenic PAHs on DNA adduct levels in both cell types was also investigated using a logistic regression model with adjustment for possible modulating effect of confounders (smoking, GSTM1, NAT2, age, plasma levels of vitamins A and E, body mass index and diet). The results showed that coke oven workers had a significantly (P < 0.05) increased adjusted Odds Ratio (OR = 4.2 and 3.9 for WBC and LYM-DNA adducts) for occurrence of higher DNA adduct levels as compared to controls. The results also showed that the relative risk of an increased prevalence of 'abnormal' values of DNA adduct levels was exposure-dose related. The influence of confounding variables was found not to be significant in this study of relatively limited size. In spite of this, the results suggest that the DNA adduct levels in LYM seem to be affected by smoking (OR = 1.8 for smokers) and are modulated by the influence of NAT2 genotypes (OR = 1.6 for slow acetylators). Our findings indicate that both cell types are generally suitable to monitor occupational exposure to PAHs, and the results suggest that coke oven workers, smoking individuals and slow acetylators sustain more genetic damage in their LYM-DNA from exposure to carcinogenic PAHs than individuals without these actors.

• MeSH
• adukty DNA krev   účinky léků   MeSH
• arylamin-N-acetyltransferasa genetika   MeSH
• dospělí MeSH
• genotyp MeSH
• glutathiontransferasa genetika   MeSH
• koks škodlivé účinky   MeSH
• kotinin moč   MeSH
• leukocyty chemie   účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• logistické modely MeSH
• lymfocyty chemie   účinky léků   MeSH
• polycyklické aromatické uhlovodíky škodlivé účinky   MeSH
• pracovní expozice * MeSH
• radioizotopy fosforu MeSH
• studie případů a kontrol MeSH
• vitaminy krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adukty DNA MeSH
• arylamin-N-acetyltransferasa MeSH
• glutathiontransferasa MeSH
• koks MeSH
• kotinin MeSH
• NAT2 protein, human MeSH Prohlížeč
• polycyklické aromatické uhlovodíky MeSH
• radioizotopy fosforu MeSH
• vitaminy MeSH

The impact of air pollution exposure on the level of total DNA adducts in human white blood cells (WBCs) was evaluated in two populations in the Czech Republic and compared to the exposure-DNA adduct relationship in other populations in the US and China in human lung cells and rodent lung tissue. The human populations examined were exposed to respirable particles (< 2.5 microm) (PM2.5) in urban, rural, and occupational settings where the particles originated from coal and petroleum fuel combustion, coke production, and other coal-tar aerosols (e.g., used in aluminum production). These particles contain carcinogenic polycyclic aromatic hydrocarbons (PAHs) that are known to form DNA adducts through covalent binding. Personal exposure to PM2.5 and PAHs were measured prior to collection of blood samples for DNA adduct analysis by 32P-postlabeling. Coke oven workers (n = 76), in 10 job categories on the top and side of a coke oven in Ostrava, CZ, were studied and compared to a different population exposed to environmental levels of PAHs from air pollution in Teplice, CZ. Personal exposures to airborne particles ranged from < 1 to more than 15,000 microg/m3 and carcinogenic PAHs exposure ranged from < 5 to > 200,000 ng/m3. At low to moderate environmental exposures to carcinogenic PAHs, DNA adduct levels in the WBCs were significantly correlated with exposure. However, at the higher occupational levels found on the coke oven, the exposure-DNA adduct relationship became non-linear. Under these high exposure conditions, the relative DNA adduct level per unit of exposure (DNA-binding potency) was significantly lower than measured at environmental exposures. This finding is consistent with observations in lung cells from bronchoalveolar lavage of humans exposed to a wide range of PAH. This same high exposure-dose non-linearity was also observed in lung DNA from rats exposed by inhalation to a coal-tar pitch aerosol. DNA adduct levels in all these cases show evidence of a form of non-linearity at high doses that has been described by Lutz (W.K. Lutz, Dose-response relationship and low dose extrapolation in chemical carcinogenesis, Carcinogenesis, 11 (1990) 1243-1247) as a superlinear dose response. This superlinear response may be due to saturation of metabolic activation enzymes, induction of either DNA repair processes or detoxification enzymes, or other mechanisms. Regardless of the mechanism, this decrease in the DNA-binding potency at moderate to high doses of PAH has important implications for dose-response extrapolation in risk assessment.

• MeSH
• adukty DNA krev   MeSH
• benzopyren analýza   toxicita   MeSH
• dehet uhelný škodlivé účinky   MeSH
• endonukleasy metabolismus   MeSH
• karcinogeny škodlivé účinky   MeSH
• kouření MeSH
• krysa rodu Rattus MeSH
• látky znečišťující vzduch v pracovním prostředí škodlivé účinky   MeSH
• látky znečišťující vzduch škodlivé účinky   MeSH
• leukocyty chemie   MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• polycyklické aromatické uhlovodíky škodlivé účinky   MeSH
• potkani Wistar MeSH
• pracovní expozice MeSH
• radioizotopy fosforu metabolismus   MeSH
• vystavení vlivu životního prostředí MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• adukty DNA MeSH
• benzopyren MeSH
• dehet uhelný MeSH
• endonukleasy MeSH
• karcinogeny MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• látky znečišťující vzduch MeSH
• polycyklické aromatické uhlovodíky MeSH
• radioizotopy fosforu MeSH

Occupational exposure to styrene was studied in nine workers of a hand lamination plant in Bohemia. Personal dosimeters were used to monitor the styrene workplace exposure, and the levels of styrene in blood and mandelic acid in urine were measured. Blood samples were taken at four occasions during a 7 month period to determine styrene-specific O6-guanine DNA adducts in lymphocytes and granulocytes, DNA strand breaks and hypoxanthine guanine phosphoribosyltransferase (HPRT) mutant frequency in T-lymphocytes. Seven administrative employees in the same factory (factory controls) and eight persons in a research laboratory (laboratory controls) were used as referents. DNA adduct levels determined by the 32P-postlabelling method in lymphocytes of laminators were remarkably constant and significantly higher (P < 0.0001) than in factory controls at all four sampling times. HPRT mutant frequencies (MF) measured by the T-cell cloning assay were higher in the laminators (17.5 x 10(-6), group mean) than in the factory controls (15.7 x 10(-6), group mean) at three of the four sampling times, but the differences were not statistically significant. However, a statistically significant (P = 0.021) difference between MF in the laminators (18.0 x 10(-6), group mean) and laboratory controls (11.8 x 10(-6), group mean) was observed at sampling time 4 (the only sampling time when this latter group was studied). This result indicates that styrene exposure may induce gene mutation in T-cells in vivo. DNA strand breaks were studied by the 'Comet assay' at the fourth sampling time. The laminators were found to have significantly higher levels of DNA strand breaks than the factory controls (P = 0.032 for tail length, TL; P = 0.007 for percentage of DNA in tail, T%; and P = 0.020 for tail moment, TM). A statistically significant correlation was also found between the levels of lymphocyte DNA adducts and all three DNA strand break parameters (TL P = 0.046; T% P = 0.026 and TM P = 0.034). On the contrary, no significant correlations were found between DNA adduct levels and the HPRT mutant frequencies or between the mutant frequencies and DNA strand breaks. Taken together, these results add further support to the genotoxic and possibly mutagenic effects of styrene exposure in vivo. However, no simple quantitative relationship seems to exist between the levels of styrene-induced DNA damage and frequency of HPRT mutation in T-lymphocytes.

• MeSH
• adukty DNA krev   MeSH
• analýza rozptylu MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• dospělí MeSH
• granulocyty účinky léků   metabolismus   MeSH
• guanin krev   MeSH
• hypoxanthinfosforibosyltransferasa genetika   MeSH
• kyseliny mandlové moč   MeSH
• leukocyty účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování životního prostředí MeSH
• mutace * MeSH
• poškození DNA * MeSH
• pracovní expozice * MeSH
• styren MeSH
• styreny škodlivé účinky   krev   MeSH
• T-lymfocyty účinky léků   enzymologie   metabolismus   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• adukty DNA MeSH
• biologické markery MeSH
• guanin MeSH
• hypoxanthinfosforibosyltransferasa MeSH
• kyseliny mandlové MeSH
• mandelic acid MeSH Prohlížeč
• styren MeSH
• styreny MeSH