caa a22 4500 445853522 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-011-0684-3 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0684-3 Modulation of urinary polycyclic aromatic hydrocarbon metabolites by enzyme polymorphisms in workers of the German Human Bitumen Study [Elektronische Daten] [Hans-Peter Rihs, Anne Spickenheuer, Evelyn Heinze, Beate Pesch, Monika Raulf-Heimsoth, Jürgen Angerer, Thomas Brüning] 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. Springer-Verlag, 2011 Bitumen nationallicence Hydroxyphenanthrenes nationallicence 1-hydroxypyrene nationallicence Polycyclic aromatic hydrocarbons nationallicence Real-time PCR nationallicence Single-nucleotide polymorphisms nationallicence Rihs Hans-Peter 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 aut Spickenheuer Anne 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 aut Heinze Evelyn 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 aut Pesch Beate 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 aut Raulf-Heimsoth Monika 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 aut Angerer Jürgen 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 aut Brüning Thomas 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 aut Archives of Toxicology Springer-Verlag 85(2011-06-01), 73-79 0340-5761 85<73 2011 85 204 https://doi.org/10.1007/s00204-011-0684-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0684-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rihs Hans-Peter 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 aut NATIONALLICENCE 700 1- Spickenheuer Anne 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 aut NATIONALLICENCE 700 1- Heinze Evelyn 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 aut NATIONALLICENCE 700 1- Pesch Beate 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 aut NATIONALLICENCE 700 1- Raulf-Heimsoth Monika 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 aut NATIONALLICENCE 700 1- Angerer Jürgen 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 aut NATIONALLICENCE 700 1- Brüning Thomas 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 aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85(2011-06-01), 73-79 0340-5761 85<73 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer