Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.
ABSTRACT 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.
- SourceAvailable from: Heiko Udo Käfferlein
[Show abstract] [Hide abstract]
- "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). "
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.Archives of Toxicology 07/2009; 83(10):947-57. DOI:10.1007/s00204-009-0444-9 · 5.08 Impact Factor
[Show abstract] [Hide abstract]
- "Zhang et al.'s  study (GM, 9.86 mmol/mol creatinine), Serdar et al.'s  study (GM, 8.47 mmol/mol creatinine), and Leng et al.'s  study, but higher than those of Zhao et al.'s  study (AM, 2.87 mmol/mol creatinine). These results show that Chinese COWs have higher levels of 1-OHP than similar workers from other industrialized western countries [Jongeneelen, 1992; Levin et al., 1995; Brescia et al., 1999; Rihs et al., 2005; Unwin et al., 2006]. In general, urinary 1-OHP levels were less than 3 mmol/mol creatinine in COWs from these other countries. "
ABSTRACT: 1-Hydroxypyrene (1-OHP) is a biomarker of recent exposure to polycyclic aromatic hydrocarbons (PAHs). We investigated whether urinary 1-OHP concentrations in Chinese coke oven workers (COWs) are modulated by job category, respirator usage, and cigarette smoking. The present cross-sectional study measured urinary 1-OHP concentrations in 197 COWs from Coking plant I and 250 COWs from Coking plant II, as well as 220 unexposed referents from Control plant I and 56 referents from Control plant II. Urinary 1-OHP concentrations (geometric mean, micromol/mol creatinine) were 5.18 and 4.21 in workers from Coking plants I and II, respectively. The highest 1-OHP levels in urine were found among topside workers including lidmen, tar chasers, and whistlers. Benchmen had higher 1-OHP levels than other workers at the sideoven. Above 75% of the COWs exceeded the recommended occupational exposure limit of 2.3 micromol/mol creatinine. Respirator usage and increased body mass index (BMI) slightly reduced 1-OHP levels in COWs (P < 0.1). Cigarette smoking significantly increased urinary 1-OHP levels in unexposed referents (P < 0.005), but had no effect in COWs (P > 0.1). Chinese COWs, especially topside workers and benchmen, are exposed to high levels of PAHs. Urinary 1-OHP concentrations appear to be modulated by respirator usage and BMI in COWs, as well as by smoking in unexposed referents.American Journal of Industrial Medicine 09/2007; 50(9):657-63. DOI:10.1002/ajim.20502 · 1.59 Impact Factor
[Show abstract] [Hide abstract]
- "There is a lack of information on the role of GSTP1 in the metabolism of PAHs. No significant influence of GSTP1 was found in Ovrebo et al.'s (1998), Alexandrie et al.'s (2000), Nerurkar et al.'s (2000), Zhang et al.'s (2001), and Rihs et al.'s (2005) studies. However, Schoket et al. (2001) found a slightly lower 1-OHP level in GSTP1 I105V VV carriers. "
ABSTRACT: Urinary 1-hydroxypyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbons (PAHs) exposure, may be influenced by metabolic gene polymorphisms. Such knowledge could benefit us in understanding the inter-individual difference in the mechanism of PAHs-induced carcinogenesis. We investigated the influence of gene polymorphisms on urinary 1-OHP concentrations in 447 coke oven workers from two coking plants in south China. After adjustment for age, plant, level of occupational exposure, body mass index, level of education, alcohol consumption, cigarette smoking and respirator usage, AhR R554K (rs2066853), UGT1A1 -3263T>G (rs4124874) and GSTP1 I105V (rs1695) were associated with urinary 1-OHP excretion with the p-value of 0.053, 0.006 and 0.021, respectively. The concentrations of urinary 1-OHP (Geometric mean, micromol/mol creatinine) in the homozygous major variant carriers and homozygous minor variant carriers for AhR R554K, UGT1A1 -3263T>G and GSTP1 I105V were listed as follows: 4.20 and 5.12, 5.11 and 3.92, 4.93 and 2.91, respectively. GSTT1 present carriers had a significantly higher urinary 1-OHP level than that in null carriers in the case with AhR R554K GA/AA carriers (5.17 vs. 3.64 micromol/mol creatinine, p=0.038), as well as in the case with UGT1A1 -3263T>G TG/GG carriers (5.67 vs. 3.38 micromol/mol creatinine, p=0.001). These results showed that AhR, UGT1A1, GSTP1 and GSTT1 polymorphisms were associated with urinary 1-OHP concentrations in Chinese coke oven workers. No influence was found in the association between urinary 1-OHP and other genetic polymorphisms such as CYP1A1, CYP1A2, CYP1B1, CYP2E1, EPHX1, EPHX2 in this population.Science of The Total Environment 08/2007; 381(1-3):38-46. DOI:10.1016/j.scitotenv.2007.02.021 · 4.10 Impact Factor