title: Modulation of urinary polycyclic aromatic hydrocarbon metabolites by enzyme polymorphisms in workers of the German Human Bitumen Study.
abstract: Data concerning the influence of sequence variants of metabolizing enzymes on the effect modulation of current exposure to vapors and aerosols of bitumen in humans are limited. To assess the influence of 18 single-nucleotide polymorphisms (SNP) in genes coding for enzymes involved in polycyclic aromatic hydrocarbon (PAH) and amine metabolism regarding their impact on urinary markers 1-hydroxpyrene (1-OHP) and the sum of 1-, 2+9-, 3-, 4-hydroxyphenanthrene (OHPHE). Based on personal ambient monitoring data for bitumen emissions, 218 German workers exposed to vapors and aerosols of bitumen during a shift and 96 German roadside construction workers without exposure to bitumen but with similar working tasks were studied. SNP determination based on DNA aliquots isolated from blood samples by real-time PCR or direct sequencing. The impact of sequence variants on the urinary levels of 1-OHP and sum of OHPHE was estimated with mixed linear models, adjusted for age, creatinine, exposure, smoking, SNP, and time of measurement. In the mixed linear model, an increasing metabolite level of OHPHE was only slightly modulated by the CC variant of the cytochrome P450 SNP CYP1A1 3801T>C (rs4646903; P = 0.051). In contrast, GSTM1 carriers showed a significant (P= 0.046) and double-mutated variants of three NAT2-specific SNP (NAT2*341CC, P = 0.06; NAT2*481TT, P = 0.06; NAT2*803GG, P = 0.042) displayed a decreasing influence on OHPHE levels. None of the SNP studied showed a significant effect on 1-OHP. The modulating SNP effects on OHPHE in the adjusted model were less pronounced when compared with the effects observed in a recent study with 170 workers occupationally exposed to PAH in German industries. This may be due to the much lower PAH exposure in the Human Bitumen Study.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr University Bochum (IPA), Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. rihs@ipa-dguv.de
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Rihs
authors.forename: Anne
authors.initials: A
authors.lastname: Spickenheuer
authors.forename: Evelyn
authors.initials: E
authors.lastname: Heinze
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Monika
authors.initials: M
authors.lastname: Raulf-Heimsoth
authors.forename: Jürgen
authors.initials: J
authors.lastname: Angerer
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols; D000395:Air Pollutants, Occupational / Q000378:metabolism* / Q000633:toxicity; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000652:urine; D003430:Cross-Sectional Studies; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004784:Environmental Monitoring; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006838:Hydrocarbons / Q000378:metabolism* / Q000633:toxicity; D019570:Inhalation Exposure / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism* / Q000652:urine; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D043922:Toxicogenetics; D055815:Young Adult
chemical_list: D000336:Aerosols; D000395:Air Pollutants, Occupational; D001191:Arylamine N-Acetyltransferase; D015415:Biomarkers; D019363:Cytochrome P-450 CYP1A1; D004798:Enzymes; D005982:Glutathione Transferase; D006838:Hydrocarbons; D011084:Polycyclic Aromatic Hydrocarbons; C006647:asphalt; C478900:NAT2 protein, human