Air pollution by carcinogenic PAHs and plasma levels of p53 and p21 WAF1 proteins

Abstract

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, 234 pg/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, 167 pg/ml versus 25 pg/ml, p < 0.001; p21 WAF1, 2690 pg/ml versus 2600 pg/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.