Internal exposure to carcinogenic polycyclic aromatic hydrocarbons and DNA damage: a null result in brief
Internal exposure to carcinogenic polycyclic aromatic hydrocarbons and DNA damage: a null result in brief
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内部暴露于致癌多环芳烃和 DNA 损伤：简要结果为无效
作者：
H. Käfferlein;B. Marczynski;P. Simon;J. Angerer;H. Rihs;M. Wilhelm;K. Straif;B. Pesch;T. Brüning
我们之前报道了接触多环芳烃 (PAH) 的焦炉、耐火材料、石墨电极和转炉工人的 171 份血液样本中 DNA 链断裂频率和 8-oxo-7,8-diHydro-20-deoxyguanosine (8-oxo-dGuo) 加合物水平。建筑工人（n = 48）被用作对照（Marczynski 等人，2009 年）。通过测定班后尿样中的 1-羟基芘 (1-OHP) 和五种羟基菲 (P OHPhe) 的总和来评估内部剂量。我们的结果清楚地表明，在群体水平上，接触过的工人的 DNA 损伤有所增加。然而，个体水平上的剂量反应关联的结果并没有揭示测量的暴露和效应之间的定量相关性。我们已经讨论了观察到的结果的几个潜在原因。简而言之，内部暴露和影响是基于单个时间点（班后样本），并且人类接触化学致癌物（如 PAH）后形成 8-oxo-dGuo 和 DNA 链断裂的动力学尚不清楚。个体暴露环境，例如不同的暴露途径（皮肤接触还是吸入）以及在工作场所可能同时接触灰尘或其他化合物，可能会导致剂量反应关联，而不是单独接触多环芳烃（Courter et al. 2007）。尽管 PAH 可以经历氧化还原循环，并且能够诱导氧化性 DNA 损伤（Park 等，2008），但血液中的 DNA 链断裂和 8-oxo-dGuo 是氧化应激的一般生物标志物，因此是途径特异性而非物质特异性。最后，PAH 是一种由致癌和非致癌化合物组成的复杂混合物，在不同行业和环境中以不同的形式存在（Rehwagen 等人，2005 年；Unwin 等人，2006 年）。 1-OHP 和 P OHPhe 是芘和菲的代谢产物，因此代表非致癌性 PAH，而不是致癌性 PAH。为了缩小个体水平上 PAH 暴露与 DNA 损伤之间缺乏关联的原因，我们重新分析了 PAH 的致癌作用。为此，我们重点关注苯并[a]芘 (B[a]P) 和萘。 B[a]P 是一种完全致癌物，在研究化合物的遗传毒性和致癌性时通常用作生物测定中的阳性对照（IARC 2010）。此外，B[a]P已被证明在啮齿类动物的肺和肝中具有最高的酶诱导效率，因此在其代谢过程中自我增强反应性亲电子和致癌中间体的形成（Elovaara等人，2007年；Skupinska等人，2007年）。啮齿动物吸入高浓度的萘已被证明具有致癌性（NTP 2000）。可用于评估 H. U. Kafferlein (&) B. Marczynski J. Angerer H.-P. 的生物标志物。 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, 德国 电子邮件：kaefferlein@ipa-dguv.de
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
DOI：
10.1093/annhyg/mep041
发表时间：
2009-08
期刊：
The Annals of occupational hygiene
影响因子：
--
作者：
J. Sobus;M. McClean;R. Herrick;S. Waidyanatha;F. Onyemauwa;L. Kupper;S. Rappaport
通讯作者：
J. Sobus;M. McClean;R. Herrick;S. Waidyanatha;F. Onyemauwa;L. Kupper;S. Rappaport
影响因子：
3.8
作者：
Courter, Lauren A.;Musatia-Jeknic, Tamara;Baird, William M.
通讯作者：
Baird, William M.