Rossner Pavel, Binkova Blanka, Milcova Alena, Solansky Ivo, Zidzik Jozef, Lyubomirova Karolina D, Farmer Peter B, Sram Radim J
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR and Health Institute of Central Bohemia, Prague, Czech Republic.
Mutat Res. 2007 Jul 1;620(1-2):34-40. doi: 10.1016/j.mrfmmm.2007.02.020. Epub 2007 Mar 3.
We analyzed the effect of exposure to carcinogenic polycyclic aromatic hydrocarbons (c-PAHs) in ambient air on the plasma levels of p53 and p21(WAF1) proteins among city policemen, bus drivers and controls in three European cities: Prague (Czech Republic), Kosice (Slovakia) and Sofia (Bulgaria). p53 and p21(WAF1) proteins are key regulators of the cell cycle and are accepted as universal markers of genotoxic stress and DNA damage. In total 204 exposed subjects (100 smokers, 104 nonsmokers) and 152 controls (54 smokers, 98 nonsmokers) were analyzed. Personal exposure to c-PAHs was evaluated using personal samplers during the working shift. The levels of p53 and p21(WAF1) proteins were assessed by ELISA assay. There were no differences between the levels of either protein between exposed and controls, or smokers and nonsmokers, in any city. However, we observed significant differences in p53 plasma levels in all subjects regardless of the exposure status between the individual cities (median values: 5, 31, 234pg/ml, p<0.001, for Prague, Kosice and Sofia, respectively). The levels correspond to the differences in exposure levels to c-PAHs and benzo[a]pyrene (B[a]P) in the individual cities. A multiple linear regression analysis confirmed that c-PAHs exposure is a variable significantly affecting levels of both proteins in all locations. When all subjects were divided into the group exposed to below-median levels of c-PAHs and the group exposed to above-median levels of c-PAHs we found significantly higher p53, as well as p21(WAF1) levels in the above-median exposure group (p53, 167pg/ml versus 25pg/ml, p<0.001; p21(WAF1), 2690pg/ml versus 2600pg/ml, p<0.05). Among all subjects p53 plasma levels were positively correlated with p21(WAF1) levels, exposure to B[a]P, c-PAHs and levels of total DNA adducts; for p21(WAF1) levels we observed the positive correlation with cotinine, c-PAHs exposure, total and B[a]P-like DNA adduct levels. In conclusion our results suggest that p53 and p21(WAF1) proteins plasma levels may be useful biomarkers of c-PAHs environmental exposure.
我们分析了欧洲三个城市（捷克共和国布拉格、斯洛伐克科希策和保加利亚索非亚）的城市警察、公交车司机及对照人群中，暴露于环境空气中致癌性多环芳烃（c-PAHs）对p53和p21（WAF1）蛋白血浆水平的影响。p53和p21（WAF1）蛋白是细胞周期的关键调节因子，被公认为遗传毒性应激和DNA损伤的通用标志物。总共分析了204名暴露者（100名吸烟者，104名非吸烟者）和152名对照者（54名吸烟者，98名非吸烟者）。在工作班次期间使用个人采样器评估个人对c-PAHs的暴露情况。通过ELISA测定法评估p53和p21（WAF1）蛋白的水平。在任何一个城市中，暴露组与对照组之间、吸烟者与非吸烟者之间的两种蛋白水平均无差异。然而，我们观察到所有受试者无论暴露状况如何，其p53血浆水平在各个城市之间存在显著差异（中位数：布拉格、科希策和索非亚分别为5、31、234pg/ml，p<0.001）。这些水平与各个城市中c-PAHs和苯并[a]芘（B[a]P）的暴露水平差异相对应。多元线性回归分析证实，c-PAHs暴露是在所有地点均显著影响两种蛋白水平的一个变量。当将所有受试者分为暴露于低于c-PAHs中位数水平的组和暴露于高于c-PAHs中位数水平的组时，我们发现高于中位数暴露组中的p53以及p21（WAF1）水平显著更高（p53，167pg/ml对25pg/ml，p<0.001；p21（WAF1），2690pg/ml对2600pg/ml，p<0.05）。在所有受试者中，p53血浆水平与p21（WAF1）水平、B[a]P暴露、c-PAHs以及总DNA加合物水平呈正相关；对于p21（WAF1）水平，我们观察到其与可替宁、c-PAHs暴露、总DNA加合物水平以及B[a]P样DNA加合物水平呈正相关。总之，我们的结果表明p53和p21（WAF1）蛋白血浆水平可能是c-PAHs环境暴露的有用生物标志物。
