title: The effect of relevant genotypes on PAH exposure-related biomarkers.
abstract: Polycyclic aromatic hydrocarbons (PAHs) in coke oven emissions cause a cancer risk to humans. In a comprehensive biomonitoring study among Estonian coke oven workers, we looked at the effect of genetic polymorphisms in metabolic enzymes on urinary mutagenicity, 1-hydroxypyrene (1-OHP) concentration in urine, and aromatic DNA adducts in white blood cells (WBCs). Coke oven workers were sampled twice (samplings I and II), and controls only once at the time of sampling I. Urinary mutagenicity was measured using the Ames test. CYP1A1, microsomal epoxide hydrolase (mEH), and glutathione S-transferase (GST) genotypes were analyzed by polymerase chain reaction (PCR). Urinary mutagenicity did not differ between exposed and controls, but those coke oven workers who were smokers had significantly higher (P=0.0002) mutagenic activity in urine than nonsmokers. Urinary mutagenicity was moderately correlated to levels of 1-OHP and aromatic DNA adducts, the P values ranging from 0.0005 to 0.002. Carriers of a variant allele in exon 4 of mEH (Arg139) had elevated urinary mutagenicity (sampling I). In addition, urine mutagenicity of persons with predicted high mEH activity was significantly higher. Smoking habit did not explain the differences observed in urinary mutagenicity between mEH phenotype or genotype subgroups. Variation in exon 3 of mEH (His113) was related to a significantly (P=0.01) higher 1-OHP concentration in exposed workers (sampling II). Workers from sampling I who had an Arg139 variation in mEH had lower levels of adducts in lymphocytes (P=0.01) than others, while airborne benzo[a]pyrene (B[a]P) and His113 variation affected interactively on adduct levels. Our study shows that a comprehensive assessment of exposure is essential for elucidation of PAH exposure at a workplace. Even at high exposures metabolic polymorphisms seem to have some effect on biomarker levels, and should be assessed in biomonitoring studies.
authors.affiliation: Institute of Occupational Health, FIN-00250 Helsinki, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Kuljukka-Rabb
authors.forename: Lars
authors.initials: L
authors.lastname: Nylund
authors.forename: Raija
authors.initials: R
authors.lastname: Vaaranrinta
authors.forename: Kirsti
authors.initials: K
authors.lastname: Savela
authors.forename: Pertti
authors.initials: P
authors.lastname: Mutanen
authors.forename: Toomas
authors.initials: T
authors.lastname: Veidebaum
authors.forename: Marja
authors.initials: M
authors.lastname: Sorsa
authors.forename: Agneta
authors.initials: A
authors.lastname: Rannug
authors.forename: Kimmo
authors.initials: K
authors.lastname: Peltonen
mesh_terms: D015415:Biomarkers / Q000032:analysis / Q000652:urine; D003077:Coke / Q000032:analysis; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D018736:DNA Adducts / Q000032:analysis; D004798:Enzymes / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008214:Lymphocytes; D008297:Male; D009152:Mutagenicity Tests; D016273:Occupational Exposure / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry* / Q000378:metabolism*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011721:Pyrenes / Q000378:metabolism
chemical_list: D015415:Biomarkers; D003077:Coke; D018736:DNA Adducts; D004798:Enzymes; D011084:Polycyclic Aromatic Hydrocarbons; D011721:Pyrenes; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C033146:1-hydroxypyrene