Georgiadis P, Kyrtopoulos S A
National Hellenic Research Foundation, Institute of Biological Research and Biotechnology, 48 Vassileos Constantinou Avenue, Athens, Greece.
Mutat Res. 1999 Jul 16;428(1-2):91-8. doi: 10.1016/s1383-5742(99)00035-6.
Direct epidemiological observations suggest that exposure to high levels of urban air pollution may result in increased risk of lung cancer, sufficient to account for a few (approximately 1-3) percent of total lung cancer incidence. Extrapolation from occupational exposure and risk data suggests that among potential carcinogens present in polluted urban air, polycyclic aromatic hydrocarbons (PAHs) may make a major contribution to air pollution-associated lung cancer risks. The use of biomarkers of genotoxocity in large-scale population studies may help to reduce the uncertainty involved in the assessment of such risks, especially those associated with relatively low pollution levels such as nowadays found in many Western cities. Increases in biomarkers of exposure to urban air PAHs as well as biomarkers of early effects have been detected in situations of relatively high levels of air pollution (e. g., ambient PAH concentrations of the order of a few tens of micrograms per cubic meter). Evidence has also been found about the modulation genetic damage accumulation in different individuals by polymorphisms in genes involved in the activation or detoxification of PAHs, especially of polymorphisms GSTM1 and CYP1A1 genes. However, the inconsistencies in the currently reported effects of genetic polymorphisms suggest that additional factors may also be important in the modulation of individual susceptibility to the accumulation of PAH-derived genetic damage. Biomarkers studies in populations exposed to relatively low ambient PAH concentrations (below 20 microg/m(3)) have not demonstrated clear dose-related effects (e.g., on DNA adduct levels), possibly because of the existence of multiple sources and routes of human exposure to PAHs in addition to inhalation of urban air (including, for example, home heating, environmental tobacco smoke and diet), and the consequent difficulty of adequately and specifically assessing atmospheric air-related exposure. This makes it imperative that molecular epidemiology studies be designed in such a way as to allow adequate assessment of exposure to urban air PAHs at the individual level and over short-, medium- and long-term time periods which correspond to the expression times of different biomarkers.
直接的流行病学观察表明，暴露于高水平的城市空气污染中可能会增加患肺癌的风险，这足以解释肺癌总发病率中约1%至3%的病例。从职业暴露和风险数据推断，在受污染的城市空气中存在的潜在致癌物中，多环芳烃（PAHs）可能是导致与空气污染相关的肺癌风险的主要因素。在大规模人群研究中使用基因毒性生物标志物可能有助于减少此类风险评估中的不确定性，尤其是与许多西方城市如今发现的相对低污染水平相关的风险。在空气污染水平相对较高的情况下（例如，环境PAH浓度达到每立方米几十微克的量级），已检测到城市空气中PAHs暴露生物标志物以及早期效应生物标志物的增加。也有证据表明，参与PAHs激活或解毒的基因中的多态性，特别是GSTM1和CYP1A1基因的多态性，会调节不同个体中遗传损伤的积累。然而，目前报道的基因多态性效应存在不一致性，这表明其他因素在调节个体对PAH衍生遗传损伤积累的易感性方面可能也很重要。对暴露于相对低环境PAH浓度（低于20微克/立方米）的人群进行的生物标志物研究尚未证明明显的剂量相关效应（例如，对DNA加合物水平的影响），这可能是因为除了吸入城市空气（包括例如家庭取暖、环境烟草烟雾和饮食）之外，人类接触PAHs还有多种来源和途径，因此难以充分且具体地评估与大气空气相关的暴露。这使得必须设计分子流行病学研究，以便能够在个体层面以及与不同生物标志物表达时间相对应的短期、中期和长期时间段内充分评估对城市空气中PAHs的暴露。
