Farmer Peter B, Singh Rajinder, Kaur Balvinder, Sram Radim J, Binkova Blanka, Kalina Ivan, Popov Todor A, Garte Seymour, Taioli Emanuela, Gabelova Alena, Cebulska-Wasilewska Antonina
Cancer Biomarkers and Prevention Group, Biocentre, University of Leicester, University Road, Leicester LE1 7RH, UK.
Mutat Res. 2003 Nov;544(2-3):397-402. doi: 10.1016/j.mrrev.2003.09.002.
Exposure to high levels of environmental air pollution is known to be associated with an increased carcinogenic risk. The individual contribution to this risk derived from specific carcinogenic chemicals within the complex mixture of air pollution is less certain, but may be explored by the use of molecular epidemiological techniques. Measurements of biomarkers of exposure, of effect and of susceptibility provide information of potential benefit for epidemiological and cancer risk assessment. The application of such techniques has been mostly concerned in the past with the carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) that are associated with particulate matter in air pollution, and has showed clear evidence of genotoxic effects, such as DNA adducts, chromosome aberrations (CA) and ras oncogene overexpression, in environmentally exposed Czech and Polish populations. We are currently extending these studies by an investigation of populations exposed to environmental pollution in three European countries, Czech Republic, Slovak Republic and Bulgaria. This pays particular attention to PAHs, but also investigates the extent of radically induced (oxidative) DNA damage in the exposed populations. Policemen, bus drivers and controls, who carried personal monitors to determine their exposures to PAHs have been studied, and blood and urine were collected. Antioxidant and dietary status were assessed in these populations. Stationary monitors were also used for ambient air monitoring. Amongst the parameters studied in the biological samples were: (a) exposure biomarkers, such as PAH adducts with DNA, p53 and p21(WAF1) protein levels, (b) oxidative DNA damage, (c) the biological effect of the exposure by measurement of chromosome damage by fluorescence in situ hybridisation (FISH) or conventional methods, and (d) polymorphisms in carcinogen metabolising and DNA repair enzymes. Repair ability was also measured by the Comet assay. In vitro systems are being evaluated to characterise the genotoxicity of the organic compounds adsorbed to air particles.
已知暴露于高水平的环境空气污染与致癌风险增加有关。空气污染复杂混合物中特定致癌化学物质对这种风险的个体贡献尚不确定，但可通过分子流行病学技术进行探索。接触、效应和易感性生物标志物的测量为流行病学和癌症风险评估提供了潜在有益信息。过去，此类技术的应用主要涉及与空气污染中的颗粒物相关的致癌多环芳烃（c-PAHs），并且在环境暴露的捷克和波兰人群中已显示出明确的基因毒性效应证据，如DNA加合物、染色体畸变（CA）和ras癌基因过表达。我们目前正在通过对捷克共和国、斯洛伐克共和国和保加利亚这三个欧洲国家暴露于环境污染的人群进行调查来扩展这些研究。这特别关注多环芳烃，但也调查暴露人群中自由基诱导（氧化）DNA损伤的程度。我们研究了携带个人监测器以确定其多环芳烃暴露情况的警察、公交车司机和对照组，并采集了血液和尿液。对这些人群的抗氧化剂和饮食状况进行了评估。还使用固定监测器进行环境空气监测。在生物样本中研究的参数包括：（a）接触生物标志物，如与DNA的多环芳烃加合物、p53和p21（WAF1）蛋白水平；（b）氧化DNA损伤；（c）通过荧光原位杂交（FISH）或传统方法测量染色体损伤来评估暴露的生物学效应；（d）致癌物代谢和DNA修复酶的多态性。还通过彗星试验测量修复能力。正在评估体外系统以表征吸附在空气颗粒上的有机化合物的基因毒性。
