Skip to main content
SpringerLink
Log in

DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect

  • Genotoxicity and Carcinogenicity
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

To study the associations between exposure to vapours and aerosols of bitumen and genotoxic effects, a cross-sectional and cross-shift study was conducted in 320 exposed workers and 118 non-exposed construction workers. Ambient air measurements were carried out to assess external exposure to vapours and aerosols of bitumen. Hydroxylated metabolites of naphthalene, phenanthrene and pyrene were measured in urine, whereas (+)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide ((+)-anti-BPDE), 8-oxo-7,8-dihydro-2′-deoxyguanosine (8oxodGuo) and DNA strand breaks were determined in blood. Significantly higher levels of 8-oxodGuo adducts and DNA strand breaks were found in both pre- and post-shift blood samples of exposed workers compared to those of the referents. No differences between exposed workers and referents were observed for (+)-anti-BPDE. Moreover, no positive associations between DNA damage and magnitude of airborne exposure to vapours and aerosols of bitumen could be observed in our study. Additionally, no relevant association between the urinary metabolites of PAH and the DNA damage in blood was observed. Overall, our results indicate increased oxidative DNA damage in workers exposed to vapours and aerosols of bitumen compared to non-exposed referents at the group level. However, increased DNA strand breaks in bitumen workers were still within the range of those found in non-exposed and healthy persons as reported earlier. Due to the lack of an association between oxidative DNA damage and exposure levels at the workplaces under study, the observed increase in genotoxic effects in bitumen workers cannot be attributed to vapours and aerosols of bitumen.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

References

  • Alexandrov K, Rojas M, Geneste O, Castegnaro M, Camus AM, Petruzzelli S, Giuntini C, Bartsch H (1992) An improved fluorometric assay for dosimetry of benzo[a]pyrene diol-epoxide-DNA adducts in smokers’ lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. Cancer Res 52:6248–6253

    PubMed  CAS  Google Scholar 

  • Boffetta P (2010) Biomarkers in cancer epidemiology: an integrative approach. Carcinogenesis 31:121–126

    Article  PubMed  CAS  Google Scholar 

  • Boffetta P, Burstyn I, Partanen T, Kromhout H, Svane O, Langård S, Järvholm B, Frentzel-Beyme R, Kauppinen T, Stücker I, Shaham J, Heederik D, Ahrens W, Bergdahl IA, Cenée S, Ferro G, Heikkilä P, Hooiveld M, Johansen C, Randem BG, Schill W (2003a) Cancer mortality among European asphalt workers: an international epidemiological study. I. Results of the analysis based on job titles. Am J Ind Med 43:18–27

    Article  PubMed  Google Scholar 

  • Boffetta P, Burstyn I, Partanen T, Kromhout H, Svane O, Langård S, Järvholm B, Frentzel-Beyme R, Kauppinen T, Stücker I, Shaham J, Heederik D, Ahrens W, Bergdahl IA, Cenée S, Ferro G, Heikkilä P, Hooiveld M, Johansen C, Randem BG, Schill W (2003b) Cancer mortality among European asphalt workers: an international epidemiological study. II. Exposure to bitumen fume and other agents. Am J Ind Med 43:28–39

    Article  PubMed  Google Scholar 

  • Boysen G, Hecht SS (2003) Analysis of DNA and protein adducts of benzo[a]pyrene in human tissues using structure-specific methods. Mutat Res 543:17–30

    Article  PubMed  CAS  Google Scholar 

  • Breuer D, Hahn J-U, Höber D, Emmel C, Musanke U, Rühl R, Spickenheuer A, Raulf-Heimsoth M, Bramer R, Seidel A, Schilling B, Heinze E, Kendzia B, Marczynski B, Welge P, Angerer J, Brüning T, Pesch B (2011) Air sampling, analytical methodology and measurement strategy for bitumen and polycyclic aromatic hydrocarbons vapours and aerosols. Arch Toxicol (in press)

  • Burczynski ME, Lin HK, Penning TM (1999) Isoform-specific induction of a human aldo-keto reductase by polycyclic aromatic hydrocarbons (PAH), electrophiles, and oxidative stress: implications for the alternative pathway of PAH activation catalyzed by human dihydrodiol dehydrogenase. Cancer Res 59:607–614

    PubMed  CAS  Google Scholar 

  • Cavallo D, Ursini CL, Bavazzano P, Cassinelli C, Frattini A, Perniconi B, Di Francesco A, Ciervo A, Rondinone B, Iavicoli S (2006) Sister chromatid exchange and oxidative DNA damage in paving workers exposed to PAHs. Ann Occup Hyg 50:211–218

    Article  PubMed  CAS  Google Scholar 

  • Chu H, Nie L, Zhu M (2008) On estimation of bivariate biomarkers with known detection limits. Environmetrics 19:301–317

    Article  Google Scholar 

  • Collins AR, Dusinská M, Gedik CM, Stĕtina R (1996) Oxidative damage to DNA: do we have a reliable biomarker? Environ Health Perspect 104(Suppl 3):465–469

    Article  PubMed  CAS  Google Scholar 

  • Dipple A, Khan QA, Page JE, Pontén I, Szeliga J (1999) DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review). Int J Oncol 14:103–111

    PubMed  CAS  Google Scholar 

  • Dizdaroglu M (2005) Base-excision repair of oxidative DNA damage by DNA glycosylases. Mutat Res 591:45–59

    PubMed  CAS  Google Scholar 

  • European Asphalt and Pavement Association (EAPA) (2005) Asphalt in figures, EAPA, Brussels. Belgium

  • Fuchs J, Hengstler JG, Boettler G, Oesch F (1996) Primary DNA damage in peripheral mononuclear blood cells of workers exposed to bitumen-based products. Int Arch Occup Environ Health 68:141–146

    Article  PubMed  CAS  Google Scholar 

  • Gedik CM, Collins A, ESCODD (European Standards Committee on Oxidative DNA Damage) (2005) Establishing the background level of base oxidation in human lymphocyte DNA: results of an interlaboratory validation study. FASEB J 19:82–84

    PubMed  CAS  Google Scholar 

  • Goetz ME, Luch A (2008) Reactive species: a cell damaging rout assisting to chemical carcinogens. Cancer Lett 266:73–83

    Article  PubMed  CAS  Google Scholar 

  • Hartlerode AJ, Scully R (2009) Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J 423:157–168

    Article  PubMed  CAS  Google Scholar 

  • IARC (1983) Polynuclear aromatic compounds, part 1: chemical, environmental and experimental data. IARC Monogr Eval Carcinog Risks Hum, vol 32. IARC, Lyon

    Google Scholar 

  • IARC (1985) Bitumen. IARC Monogr Eval Carcinog Risks Chem Hum Overall evaluations of the carcinogenicity: an updating of IARC monographs, vol 1–42

  • IARC (2001) IARC epidemiological study of cancer mortality among European asphalt workers. IARC internal report no. 01/003

  • IARC (2002) IARC monograph on ‘Some traditional herbal medicines, some mycotoxins, naphthalene and styrene’, vol 82. International Agency for Research on Cancer, Lyon

    Google Scholar 

  • IARC (2011) IARC Monograph on ‘Bitumen and bitumen fumes, and some heterocyclic polycyclic aromatic hydrocarbons’, vol 103. International Agency for Research on Cancer, Lyon

  • Jongeneelen FJ (1997) Methods for routine biological monitoring of carcinogenic PAH-mixtures. Sci Total Environ 199:141–149

    Article  PubMed  CAS  Google Scholar 

  • Kennedy LJ, Moore K Jr, Caulfield JL, Tannenbaum SR, Dedon PC (1997) Quantitation of 8-oxoguanine and strand breaks produced by four oxidizing agents. Chem Res Toxicol 10:386–392

    Article  PubMed  CAS  Google Scholar 

  • Klaunig JE, Xu Y, Isenberg JS, Bachowski S, Kolaja KL, Jiang J, Stevenson DE, Walborg EF Jr (1998) The role of oxidative stress in chemical carcinogenesis. Environ Health Perspect 106(Suppl 1):289–295

    Article  PubMed  CAS  Google Scholar 

  • Lindberg HK, Väänänen V, Järventaus H, Suhonen S, Nygren J, Hämeilä M, Valtonen J, Heikkilä P, Norppa H (2008) Genotoxic effects of fumes from asphalt modified with waste plastic and tall oil pitch. Mutat Res 653:82–90

    PubMed  CAS  Google Scholar 

  • Lintelmann J, Angerer J (1999) PAH metabolites. In: Angerer J, Schaller KH (eds) Analyses of hazardous substances in biological materials, vol 6. Wiley, Weinheim, pp 163–187

    Google Scholar 

  • Luch A (2005) Nature and nurture–lessons from chemical carcinogenesis. Nat Rev Cancer 5:113–125

    Article  PubMed  CAS  Google Scholar 

  • Machado ML, Beatty PW, Fetzer JC, Glickman AH, McGinnis EL (1993) Evaluation of the relationship between PAH content and mutagenic activity of fumes from roofing and paving asphalts and coal tar pitch. Fundam Appl Toxicol 21:492–499

    Article  PubMed  CAS  Google Scholar 

  • Marczynski B, Rozynek P, Elliehausen HJ, Korn M, Baur X (1997) Detection of 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, in white blood cells of workers occupationally exposed to styrene. Arch Toxicol 71:496–500

    Article  PubMed  CAS  Google Scholar 

  • Marczynski B, Rihs HP, Rossbach B, Hölzer J, Angerer J, Scherenberg M, Hoffmann G, Brüning T, Wilhelm M (2002) Analysis of 8-oxo-7,8-dihydro-2′-deoxyguanosine and DNA strand breaks in white blood cells of occupationally exposed workers: comparison with ambient monitoring, urinary metabolites and enzyme polymorphisms. Carcinogenesis 23:273–281

    Article  PubMed  CAS  Google Scholar 

  • Marczynski B, Raulf-Heimsoth M, Preuss R, Kappler M, Schott K, Pesch B, Zoubek G, Hahn JU, Mensing T, Angerer J, Käfferlein HU, Brüning T (2006) Assessment of DNA damage in WBCs of workers occupationally exposed to fumes and aerosols of bitumen. Cancer Epidemiol Biomark Prev 15:645–651

    Article  CAS  Google Scholar 

  • Marczynski B, Raulf-Heimsoth M, Spickenheuer A, Mensing T, Welge P, Förster K, Angerer J, Pesch B, Bramer R, Käfferlein HU, Breuer D, Hahn JU, Brüning T (2007) Ambient and biological monitoring of exposure and genotoxic effects in mastic asphalt workers exposed to fumes of bitumen. J Occup Environ Hygiene 4(Suppl 1):127–136

    Article  CAS  Google Scholar 

  • McClean MD, Rinehart RD, Ngo L (2004) Urinary 1-hydroxypyrene and polycyclic aromatic hydrocarbon exposure among asphalt paving workers. Ann Occup Hyg 48:565–578

    Article  PubMed  CAS  Google Scholar 

  • Møller P (2006) Assessment of reference values for DNA damage detected by the comet assay in human blood cell DNA. Mutat Res 612:84–104

    Article  PubMed  Google Scholar 

  • National Toxicology Program (NTP) (2000) Toxicology and carcinogenesis studies of naphthalene (CAS 91–20-3) in F344/N rats (inhalation studies). Natl Toxicol Program Tech Rep Ser 500:1–173

    Google Scholar 

  • NIOSH (2001) Health effects of occupational exposure to asphalt. DHHS (NIOSH) Publication No. 2001-110, Cincinnati, USA

  • Östling O, Johanson KJ (1984) Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem Biophys Res Commu 123:291–298

    Article  Google Scholar 

  • Partanen T, Boffetta P (1994) Cancer risk in asphalt workers and roofers: review and meta-analysis of epidemiologic studies. Am J Ind Med 26:721–740

    Article  PubMed  CAS  Google Scholar 

  • Pesch B, Kappler M, Straif K, Marczynski B, Preuss R, Rossbach B, Rihs HP, Weiss T, Rabstein S, Pierl C, Scherenberg M, Adams A, Käfferlein HU, Angerer J, Wilhelm M, Seidel A, Brüning T (2007) Dose-response modeling of occupational exposure to polycyclic aromatic hydrocarbons with biomarkers of exposure and effect. Cancer Epidemiol Biomark Prev 16:1863–1873

    Article  CAS  Google Scholar 

  • Pesch B, Spickenheuer A, Kendzia B, Schindler BK, Welge P, Marczynski B, Rihs H-P, Raulf-Heimsoth M, Angerer J, Brüning T (2011) Urinary metabolites of polycyclic aromatic hydrocarbons in workers exposed to vapours and aerosols of bitumen. Arch Toxicol (in press)

  • Pouget JP, Ravanat JL, Douki T, Richard MJ, Cadet J (1999) Measurement of DNA base damage in cells exposed to low doses of γ-radiation: comparison between the HPLC-EC and comet assays. Int J Radiat Biol 75:51–58

    Article  PubMed  CAS  Google Scholar 

  • Raulf-Heimsoth M, Pesch B, Rühl R, Brüning T (2011) The human bitumen study: executive summary. Arch Toxicol (in press)

  • Rojas M, Alexandrov K, Auburtin G, Wastiaux-Denamur A, Mayer L, Mahieu B, Sebastien P, Bartsch H (1995) anti-benzo[a]pyrene diolepoxide–DNA adduct levels in peripheral mononuclear cells from coke oven workers and the enhancing effect of smoking. Carcinogenesis 16:1373–1376

    Article  PubMed  CAS  Google Scholar 

  • Rojas M, Alexandrov K, Cascorbi I, Brockmöller J, Likhachev A, Pozharisski K, Bouvier G, Auburtin G, Mayer L, Kopp-Schneider A, Roots I, Bartsch H (1998) High benzo[a]pyrene diol epoxide DNA adduct levels in lung and blood cells from subjects with combined CYP1A1 MspI/Msp/I-GSTM1*0/*0 genotypes. Pharmacogenetics 8:109–118

    Article  PubMed  CAS  Google Scholar 

  • Royston P, Sauerbrei W (2008) Multivariable model-building: a pragmatic approach to regression analysis based on fractional polynomials for continuous variables. Wiley, Chichester

    Google Scholar 

  • Scherer G, Meger-Kossien I, Angerer J, Knecht U (2001) Cotinine. In: Angerer J, Schaller KH (eds) Analyses of hazardous substances in biological materials, vol 7. Wiley, Weinheim, pp 171–189

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  PubMed  CAS  Google Scholar 

  • Sivak A, Niemeier R, Lynch D, Beltis K, Simon S, Salomon R, Latta R, Belinky B, Menzies K, Lunsford A, Cooper C, Ross A, Bruner R (1997) Skin carcinogenicity of condensed asphalt roofing fumes and their fractions following dermal application to mice. Cancer Lett 117:113–123

    Article  PubMed  CAS  Google Scholar 

  • Sobus JR, McClean MD, Herrick RF, Waidyanatha S, Nylander-French LA, Kupper LL, Rappaport SM (2009a) Comparing urinary biomarkers of airborne and dermal exposure to polycyclic aromatic compounds in asphalt-exposed workers. Ann Occup Hyg 53:561–571

    Article  PubMed  CAS  Google Scholar 

  • Sobus JR, Waidyanatha S, McClean MD, Herrick RF, Smith TJ, Garshick E, Laden F, Hart JE, Zheng Y, Rappaport SM (2009b) Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons. Occup Environ Med 66:99–104

    Article  PubMed  CAS  Google Scholar 

  • Spencer JP, Jenner A, Aruoma OI, Cross CE, Wu R, Halliwell B (1996) Oxidative DNA damage in human respiratory tract epithelial cells. Time course in relation to DNA strand breakage. Biochem Biophys Res Commun 224:17–22

    Article  PubMed  CAS  Google Scholar 

  • Spickenheuer A, Rühl R, Höber D, Raulf-Heimsoth M, Marczynski B, Welge P, Breuer D, Gabriel S, Musanke U, Rode P, Heinze E, Kendzia B, Bramer R, Knecht U, Hahn J-U, Brüning T, Pesch B (2011) Levels and determinants of exposure to vapours and aerosols of bitumen. Arch Toxicol (in press)

  • Straif K, Baan R, Grosse Y, Secretan B, El Ghissassi F, Cogliano V, WHO International Agency for Research on Cancer Monograph Working Group (2005) Carcinogenicity of polycyclic aromatic hydrocarbons. Lancet Oncol 6:931–932

    Article  PubMed  Google Scholar 

  • Taussky HH (1954) A micro-colorimetric determination of creatinine in urine by the Jaffey’s reaction. J Biol Chem 208:853–861

    PubMed  CAS  Google Scholar 

  • Toraason M, Hayden C, Marlow D, Rinehart R, Mathias P, Werren D, Olsen LD, Neumeister CE, Mathews ES, Cheever KL, Marlow KL, DeBord DG, Reid TM (2001) DNA strand breaks, oxidative damage, and 1-OH pyrene in roofers with coal-tar pitch dust and/or asphalt fume exposure. Int Arch Occup Environ Health 74:396–404

    Article  PubMed  CAS  Google Scholar 

  • Watters JL, Satia JA, da Costa KA, Boysen G, Collins LB, Morrow JD, Milne GL, Swenberg JA (2009) Comparison of three oxidative stress biomarkers in a sample of healthy adults. Biomarkers 14:587–595

    Article  PubMed  CAS  Google Scholar 

  • Welge P, Marczynski B, Raulf-Heimsoth M, Spickenheuer A, Kendzia B, Heinze E, Angerer J, Käfferlein HU, Pesch B, Brüning T (2011) Assessment of micronuclei in lymphocytes from workers exposed to vapours and aerosols of bitumen. Arch Toxicol (in press)

  • Wild CP (2005) Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomark Prev 14:1847–1850

    Article  CAS  Google Scholar 

  • World Health Organisation (WHO), Asphalt (Bitumen) (2004) Concise International Chemical Assessment Document 59, WHO, Geneva

Download references

Acknowledgments

The 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 e.V., Concawe, Zentralverband des Deutschen Dachdeckerhandwerks, Industrieverband Bitumen-, Dach- und Dichtungsbahnen e.V., 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 Hans-Jürgen Schicker. We thank Anja Erkes, Brigitta Vosshans and Tina Teschner for technical assistance.

Author information

Authors and Affiliations

  1. 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

    Boleslaw Marczynski, Monika Raulf-Heimsoth, Anne Spickenheuer, Beate Pesch, Benjamin Kendzia, Thomas Mensing, Beate Engelhardt, Eun-Hyun Lee, Birgit K. Schindler, Evelyn Heinze, Peter Welge, Rainer Bramer, Jürgen Angerer, Heiko U. Käfferlein & Thomas Brüning

  2. Institute and Outpatient Clinic of Occupational, Social- and Environmental Medicine, University of Erlangen-Nuremberg, Schillerstraße 25/29, Erlangen, Germany

    Jürgen Angerer

  3. Institute for Occupational Safety of the German Social Accident Insurance (IFA), Alte Heerstrasse 111, Sankt Augustin, Germany

    Dietmar Breuer

Authors
  1. Boleslaw Marczynski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Monika Raulf-Heimsoth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne Spickenheuer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beate Pesch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Benjamin Kendzia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Thomas Mensing
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Beate Engelhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Eun-Hyun Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Birgit K. Schindler
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Evelyn Heinze
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Peter Welge
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rainer Bramer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jürgen Angerer
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Dietmar Breuer
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Heiko U. Käfferlein
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Thomas Brüning
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Boleslaw Marczynski.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marczynski, B., Raulf-Heimsoth, M., Spickenheuer, A. et al. DNA adducts and strand breaks in workers exposed to vapours and aerosols of bitumen: associations between exposure and effect. Arch Toxicol 85 (Suppl 1), 53–64 (2011). https://doi.org/10.1007/s00204-011-0682-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-011-0682-5

Keywords

Search

Navigation