Internal exposure to carcinogenic polycyclic aromatic hydrocarbons and DNA damage: a null result in brief

Abstract

We previously reported DNA strand break frequencies and adduct levels of 8-oxo-7,8-dihydro-20-deoxyguanosine (8-oxo-dGuo) in 171 blood samples of coke oven, refractory, graphite electrode, and converter workers exposed to polycyclic aromatic hydrocarbons (PAH). Construction workers (n = 48) were used as controls (Marczynski et al. 2009). Internal dose was assessed by the determination of 1-hydroxypyrene (1-OHP) and the sum of five hydroxyphenanthrenes ( P OHPhe) in post-shift urine samples. Our results clearly indicated increased DNA damage in exposed workers on a group level. The results of the dose–response associations on the individual level, however, did not reveal quantitative correlations between measured exposures and effects. We have discussed several potential reasons for the observed results. In brief, internal exposure and effect was based on single time points (post-shift samples), and kinetics for the formation of 8-oxo-dGuo and DNA strand breaks after exposure to chemical carcinogens such as PAH are not known in detail in humans. The individual exposure circumstances such as varying routes of exposures (dermal vs. inhalation) and potential co-exposures to dust or other chemical compounds at the workplace may have contributed to the dose–response association rather than exposure to PAH alone (Courter et al. 2007). Although PAH can undergo redox cycling and are capable of inducing oxidative DNA damage (Park et al. 2008), DNA strand breaks and 8-oxo-dGuo in blood are general biomarkers of oxidative stress, thus being pathwayspecific rather than substance-specific. Finally, PAH are a complex mixture consisting of carcinogenic and non-carcinogenic compounds and exist in varying profiles in different industries and the environment (Rehwagen et al. 2005; Unwin et al. 2006). 1-OHP and P OHPhe are metabolites of pyrene and phenanthrene, thus representing noncarcinogenic PAH rather than carcinogenic PAH. In order to narrow down the reasons for the lacking association between exposures to PAH and DNA damage on the individual level, we re-analyzed the role of carcinogenic PAH. For this purpose, we focused on benzo[a]pyrene (B[a]P) and naphthalene. B[a]P is a complete carcinogen and often used as a positive control in bioassays when studying genotoxicity and carcinogenicity of chemical compounds (IARC 2010). In addition, B[a]P has been shown to have the highest enzyme inducing efficiency in the lung and liver of rodents, thus self-enhancing the formation of reactive electrophilic and carcinogenic intermediates during its metabolism (Elovaara et al. 2007; Skupinska et al. 2007). Naphthalene has been shown to be carcinogenic in rodents at high concentrations after inhalation (NTP 2000). Available biomarkers to assess H. U. Kafferlein (&) B. Marczynski J. Angerer H.-P. Rihs B. Pesch T. Bruning Institut fur Pravention und Arbeitsmedizin der Deutschen Gesetzlichen Unfallversicherung, Institut der Ruhr Universitat Bochum (IPA), Burkle-de-la-Camp Platz 1, 44789 Bochum, Germany e-mail: kaefferlein@ipa-dguv.de