Occupational exposure to polycyclic aromatic hydrocarbons in German industries: association between exogenous exposure and urinary metabolites and its modulation by enzyme polymorphisms.
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.
Rihs
Hans-Peter
HP
Berufsgenossenschaftliches Forschungsinstitut für Arbeitsmedizin (BGFA), Ruhr University of Bochum, Buerkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. rihs@bgfa.de
Pesch
Beate
B
Kappler
Martin
M
Rabstein
Sylvia
S
Rossbach
Bernd
B
Angerer
Jürgen
J
Scherenberg
Michael
M
Adams
Ansgar
A
Wilhelm
Michael
M
Seidel
Albrecht
A
Brüning
Thomas
T
D000328:Adult; D000395:Air Pollutants, Occupational / Q000506:poisoning / Q000652:urine*; D003367:Cotinine / Q000652:urine; D003404:Creatinine / Q000652:urine; D003430:Cross-Sectional Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000378:metabolism; D005858:Germany; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D010616:Phenanthrenes / Q000378:metabolism; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning / Q000652:urine*; D011110:Polymorphism, Genetic; D011721:Pyrenes / Q000378:metabolism; D012907:Smoking
D000395:Air Pollutants, Occupational; D007527:Isoenzymes; D010616:Phenanthrenes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; C031181:phenanthrene; D003577:Cytochrome P-450 Enzyme System; C030984:pyrene; D003404:Creatinine; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; D003367:Cotinine