The effect of relevant genotypes on PAH exposure-related biomarkers

In regulatory toxicology, the dose-response relationship between occupational exposure and biomarkers is of importance in setting threshold values. We analyzed the relationships between occupational exposure to polycyclic aromatic hydrocarbons (PAH) and various biomarkers of internal exposure and DNA damage with data from 284 highly exposed male workers. Personal exposure to phenanthrene and other PAHs was measured during shift and correlated with the sum of 1À, 2+9À, 3À, and 4-hydroxyphenanthrenes in post-shift urine. PAHs and hydroxyphenanthrenes were associated with DNA damage assessed in WBC as 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine/10 6 dGuo and strand breaks by Comet assay as Olive tail moment. Hydroxyphenanthrenes correlated with phenanthrene (Spearman r s = 0.70; P < 0.0001). No correlations could be found between strand breaks and exposure (r s = 0.01, P < 0.0001 for PAHs; r s = À0.03, P = 0.68 for hydroxyphenanthrenes). Correlations with 8-oxo-7,8-dihydro-2 ¶-deoxyguanosine/10 6 dGuo were weakly negative (r s = À0.22, P = 0.004 for PAHs) or flat (r s = À0.08, P = 0.31 for hydroxyphenanthrenes). Linear splines were applied to assess the relationships between the log-transformed variables. All regression models were adjusted for smoking and type of industry. For hydroxyphenanthrenes, 51.7% of the variance could be explained by phenanthrene and other predictors. Up to 0.77 Mg/m 3 phenanthrene, no association could be found with hydroxyphenanthrenes. Above that point, hydroxyphenanthrenes increased by a factor of 1.47 under a doubling of phenanthrene exposure (slope, 0.56; 95% confidence interval, 0.47-0.64). Hydroxyphenanthrenes may be recommended as biomarker of occupational PAH exposure, whereas biomarkers of DNA damage in blood did not show a dose-response relation to PAH exposure. (Cancer Epidemiol Biomarkers Prev 2007;16(9):1863 -73)

Section: Discussionsupporting

confidence: 47%

Dose-Response Modeling of Occupational Exposure to Polycyclic Aromatic Hydrocarbons with Biomarkers of Exposure and Effect

Pesch

Kappler

Straif³

et al. 2007

“…Although several lines of evidence showed that variant genotypes of cytochrome P450 such as CYP1A1 and CYP2E1 could modify the metabolism of PAH in coke-oven workers (24)(25)(26), other studies reported no correlations between cytochrome P450 polymorphism and urinary 1-OHP level (9,(27)(28)(29). Therefore, it is hard to interpret the relation between cytochrome P450 polymorphism and urinary 1-OHP level.…”

Section: Discussionmentioning

confidence: 99%

Association of Aryl Hydrocarbon Receptor Gene Polymorphisms and Urinary 1-Hydroxypyrene in Polycyclic Aromatic Hydrocarbon–Exposed Workers

Peng

Leng²,

Cheng³

et al. 2008

Polycyclic aromatic hydrocarbons (PAH) in coke oven emissions could cause lung cancer in human. Individual's genotype of the metabolic enzymes and early biological changes were known to be associated with the susceptibility of cancer development. Knowledge of metabolic gene polymorphisms, which affect on the urinary 1-hydroxypyrene (1-OHP), could benefit us in understanding the interindividual difference in the mechanism of PAH-induced carcinogenesis. In this study, we investigated the association of aryl hydrocarbon receptor (AhR) gene polymorphisms and urinary 1-OHP. One hundred forty-seven workers exposed to PAH and 69 nonexposure workers were recruited. Seven tagging single nucleotide polymorphisms in AhR gene were selected by pariwise r 2 method and minor allele frequency cutoff of 0.05 from Chinese genotype data in HapMap project. These seven tagging single nucleotide polymorphisms were genotyped by PCR-based methods. Multivariate analysis of covariance revealed that the levels of 1-OHP in PAH-exposed workers carrying genotype CT were lower than workers carrying wild genotype TT at loci rs10250822 and rs2282885 of AhR gene (P = 0.032 and 0.044, respectively). In PAH-exposed workers, the urinary 1-OHP levels showed a linear correlation (P trend = 0.041) with the genotypes at locus rs2282885, especially in low and moderate exposure groups. In contrast, no significant association was found between urinary 1-OHP level and AhR genotypes among nonexposed workers. Our findings indicated that polymorphisms of AhR gene were associated with the level of 1-OHP among PAH-exposed workers, suggesting that AhR-mediated signaling might contribute to individual susceptibility to PAH exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1702 -8)

“…Glutathione S-transferase (GSTM1) genotype has been shown to influence the association between PAH exposure and 1-OHPG levels in urine (25,40). Several genetic polymorphisms, including a cytochrome P450 variant (CYP1A1), glutathione S-transferases (GSTT1 and GSTM1), N-acetyltransferase (NAT2), and an epoxide hydrolase (mEH3), have also been related to variation in 1-hydroxypyrene levels in urine (42,(66)(67)(68)(69).…”

Section: Discussionmentioning

confidence: 99%

Estimating Exposure to Polycyclic Aromatic Hydrocarbons: A Comparison of Survey, Biological Monitoring, and Geographic Information System–Based Methods

Gunier

Reynolds

Hurley

et al. 2006

Our objective was to compare polycyclic aromatic hydrocarbon (PAH) exposure estimates based on survey, biological monitoring, and geographic information system (GIS) methods. The 304 participants in this study supplied a urine sample and completed questionnaires about exposure to potential PAH sources. We assayed urine samples for 1-hydroxypyrene-O -glucuronide (1-OHPG), the major metabolite of pyrene, a common PAH. We used a GIS to estimate traffic exhaust exposure using vehicle count data at the residence and workplace. The five subjects who reported smoking during the 48-hour period had median 1-OHPG concentrations 10-fold that of nonsmokers (1.6 versus 0.16 pmol/mL; P = 0.01). Among nonsmokers, those who reported eating grilled, roasted, or broiled meat had significantly higher 1-OHPG concentrations than those who did not reported eating meat prepared by these methods (0.25 versus 0.06 pmol/mL; P = 0.02). Nonsmokers who reported traveling on roads for z3 hours during the 48-hour period also had significantly higher 1-OHPG levels than those who traveled <3 hours (0.23 versus 0.11 pmol/ mL; P = 0.03). 1-OHPG levels were also correlated with hours of secondhand smoke exposure among nonsmokers (P = 0.04). In this study, 1-OHPG urine concentrations were not associated with self-reported exposures to cooking smoke, wood burning, or traffic levels near the home or to traffic density or urban/rural status determined using a GIS. Self-reported indicators of residential proximity to high traffic volume were, however, associated with GIS traffic density measures. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1376 -81)