Occupational exposure to polycyclic aromatic hydrocarbons in German industries: Association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms

Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
Toxicology Letters (Impact Factor: 3.26). 08/2005; 157(3):241-55. DOI: 10.1016/j.toxlet.2005.02.012
Source: PubMed


A cross-sectional study was conducted in 170 German workers exposed to polycyclic aromatic hydrocarbons (PAH) to investigate the role of 11 polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, GSTM1, GSTT1, and GSTP1 in the association between occupational exposure to PAH and urinary PAH metabolites. Polymorphisms were genotyped with real-time PCR. Exposure to 16 PAH was measured by personal air sampling. Urinary concentrations of 1-hydroxypyrene (1-OHP) and the sum of 1-, 2+9-, 3-, and 4-hydroxyphenanthrenes (OHPhe) were determined post-shift. Urinary 1-OHP and OHPhe correlated significantly with exogenous pyrene (Spearman r=0.52, p<0.0001) and phenanthrene (Spearman r=0.72, p<0.0001), respectively. ANCOVA was applied to investigate potential predictors of the metabolite levels. Current smoking and type of industry turned out to be predictors of 1-OHP but not of OHPhe. CYP1A1 3801TC carriers showed 1.6-fold higher OHPhe levels than 3801TT carriers (p=0.03). EPHX1 113HH was associated with higher and 139RR with lower metabolite levels when compared with the corresponding reference genotypes (113YY; 139HH). In comparison to GSTP1 114AA, carriers of the V allele had 1.5-fold higher 1-OHP (p=0.03) and 2-fold higher OHPhe concentrations (p=0.001). OHPhe turned out to be also a suitable biomarker of occupational PAH exposure. The association with ambient PAH exposure and the influence of polymorphisms was more pronounced for OHPhe.

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    • "This opens up opportunities to assess the importance of epigenetics as a functional modifier of the genome and a key determinant of disease risk and etiology. With regard to PAHs the main recent findings are summarized in Figure 5. Rihs et al. (2005) showed that specific polymorphisms in genes coding for PAHs-metabolizing enzymes, including CYP1A1, mEH, and GSTP1 may modulate PAHsmetabolite excretion. The identification of genotypes associated with a higher level of metabolites may indicate a more rapid PAHs metabolism, as well as an overload of the urinary bladder epithelium, which may result in increased toxicity. "
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    ABSTRACT: DNA sequence and genetic factors alone cannot fully explain the many processes implicated in diseases initiation and development. It is now well understood that additional factors are involved in a final resulting phenotype. Epigenetic modifications, heritable changes not affecting the DNA sequence, are a key phenomenon at the basis of normal growth and differentiation. However, these can be defective leading to diseases, such as cancer. An increasing body of literature reports the environmental and occupational exposure to a mixture of natural and man-produced substances leading to epigenetic alterations. The identification of key genetic and/or epigenetic events involved in chemical carcinogenesis is an important step towards the discovery of biomarkers that can be used to evaluate the exposure, predict biological effects, and prevent adverse health consequences. Here, we focus on epidemiological studies to review the most recent advances in understanding genetic and epigenetic factors in relation to particulate matter, benzene and polycyclic aromatic hydrocarbons exposure.
    No preview · Article · Oct 2015 · Toxicological Sciences
    • "2.9 μmol/mol- Cr) by Trejo-Acevedo et al. (2012). The urinary 1-OHPyr values reported in this study of both cohorts were higher than those previously studies on the kitchen workers (1.25 median μmol/mol-Cr; Wang et al. 2011), coke oven workers (1.8 μmol/mol-Cr, Rihs et al. 2005), and sugarcane workers reported by Prado et al. 2012 (1.27 μmol/mol-Cr) (Table 3). The current values of β-naphthol ranged between 0.42 and 12.1 μmol mol-Cr −1 in exposed subjects, which were higher than pre-and post-shift urine samples of bus garage workers (Kuusimaki et al. 2004), foundry workers in Taiwan (Lee et al. 2010), taxi drivers and police officers in Thailand (Chetiyanukornkul et al. 2006). "
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    ABSTRACT: The main aim of this study was to evaluate and compare the cooking fumes/smoke exposure of household women and professional workers in indoor and semi-outdoor environments, respectively, by using clinico-chemical parameters and PAHs biomarkers. Female (WR n=60) and male “cooks” (WC n=60) exposed to the combustion emission of fuel wood and coal in rural/sub-urban areas of Pakistan were recruited in this study and compared to non- exposed female and male groups (CF and CM, n=32 and 34 respectively). Urinary level of PAHs exposure biomarkers including 1-hyroxypyrene (1-OHPyr), α–naphthol and β-naphthol were analyzed together with serum c-reactive proteins (CRP), white blood cells (WBCs), hemoglobin (Hb), red blood cells (RBC) and platelet count (PLT), as biomarkers of effect. In addition, blood superoxide dismutase (SOD) and urinary level of 8-hydroxydeoxyguanosine (8-OHdG) were evaluated to determine the oxidative stress and DNA damage, respectively. A questionnaire was used to document demographic, health and exposure-related information. The results showed that urinary β-naphthol was almost 44 % higher in WR subjects than WC (median 7.69 vs. 3.39 µmol mol-Cr-1, respectively; P = 0.01) and respective controls (CF). Higher urinary 8-OHdG were measured in WR (71.1 ng mg-Cr-1) than WC (56.37 ng mg-Cr-1) (P<0.001), and lower life status and higher degree of headache were observed in WR than WC. In male-subjects, however, a low Hb, and high WBC (8.29×103 µL-1, ranging between 6.1 and 10.6×103 µL-1) were observed in comparison with CM. The study shows that WC subjects used larger amount of fuel and were subjected to prolonged exposure. It was concluded that the role of ventilation is fundamental and WR were more exposed to PAHs despite the fact that WC spent more time in cooking (due to occupational requirement) than WR.
    No preview · Article · Aug 2015 · Environmental Science and Pollution Research
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    • "Here, a nationwide cross-sectional study in Germany was conducted to analyze exposure to PAH and DNA damage. Previous reports in our cohort focused on dose–response associations and the inXuence of polymorphic genes (Pesch et al. 2007; Rihs et al. 2005). We focused on PAH exposure and eVects by occupational setting (type of industry). "
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    ABSTRACT: Exposure to polycyclic aromatic hydrocarbons (PAH) and DNA damage were analyzed in coke oven (n = 37), refractory (n = 96), graphite electrode (n = 26), and converter workers (n = 12), whereas construction workers (n = 48) served as referents. PAH exposure was assessed by personal air sampling during shift and biological monitoring in urine post shift (1-hydroxypyrene, 1-OHP and 1-, 2 + 9-, 3-, 4-hydroxyphenanthrenes, SigmaOHPHE). DNA damage was measured by 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and DNA strand breaks in blood post shift. Median 1-OHP and SigmaOHPHE were highest in converter workers (13.5 and 37.2 microg/g crea). The industrial setting contributed to the metabolite concentrations rather than the air-borne concentration alone. Other routes of uptake, probably dermal, influenced associations between air-borne concentrations and levels of PAH metabolites in urine making biomonitoring results preferred parameters to assess exposure to PAH. DNA damage in terms of 8-oxo-dGuo and DNA strand breaks was higher in exposed workers compared to referents ranking highest for graphite-electrode production. The type of industry contributed to genotoxic DNA damage and DNA damage was not unequivocally associated to PAH on the individual level most likely due to potential contributions of co-exposures.
    Full-text · Article · Jul 2009 · Archives of Toxicology
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