Journal Title
Title of Journal: Arch Toxicol
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Abbravation: Archives of Toxicology
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Publisher
Springer-Verlag
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Authors: HansPeter Rihs Anne Spickenheuer Evelyn Heinze Beate Pesch Monika RaulfHeimsoth Jürgen Angerer Thomas Brüning
Publish Date: 2011/02/26
Volume: 85, Issue: 1, Pages: 73-79
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 singlenucleotide polymorphisms SNP in genes coding for enzymes involved in polycyclic aromatic hydrocarbon PAH and amine metabolism regarding their impact on urinary markers 1hydroxpyrene 1OHP and the sum of 1 2+9 3 4hydroxyphenanthrene 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 realtime PCR or direct sequencing The impact of sequence variants on the urinary levels of 1OHP 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 3801TC rs4646903 P = 0051 In contrast GSTM1 carriers showed a significant P= 0046 and doublemutated variants of three NAT2specific SNP NAT2341CC P = 006 NAT2481TT P = 006 NAT2803GG P = 0042 displayed a decreasing influence on OHPHE levels None of the SNP studied showed a significant effect on 1OHP 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 StudyThe Human Bitumen Study was initiated by the German Committee for Hazardous Substances AGS and the German Bitumen Forum and financially supported by German Social Accident Insurance DGUV Eurobitume Deutscher Asphaltverband eV Concawe Zentralverband des Deutschen Dachdeckerhandwerks Industrieverband Bitumen Dach und Dichtungsbahnen eV Berufsgenossenschaft Rohstoffe und Chemische Industrie BG RCI and Aksys GmbH Beratungsstelle Gussasphaltanwendungen bga BG BAU Arbeitsgemeinschaft der Bitumenindustrie Arbit We thank all workers having participated in the Human Bitumen Study We gratefully acknowledge the support of the field team especially Anne Flagge Anja Molkenthin Bianca Wachter Dieter Höber Gerd Zoubek and in parts of the study Klaus Schott † and HansJürgen Schicker
Keywords:
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