Air pollution by carcinogenic PAHs and plasma levels of p53 and p21(WAF1) proteins.
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.
Rossner
Pavel
P
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine, AS CR and Health Institute of Central Bohemia, Prague, Czech Republic. prossner@biomed.cas.cz
Binkova
Blanka
B
Milcova
Alena
A
Solansky
Ivo
I
Zidzik
Jozef
J
Lyubomirova
Karolina D
KD
Farmer
Peter B
PB
Sram
Radim J
RJ
D000328:Adult; D000368:Aged; D000397:Air Pollution; D001564:Benzo(a)pyrene / Q000633:toxicity; D002274:Carcinogens, Environmental / Q000633:toxicity*; D003367:Cotinine / Q000097:blood; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000097:blood*; D018736:DNA Adducts / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016495:Police; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000097:blood*
C493956:CDKN1A protein, human; D002274:Carcinogens, Environmental; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53; D001564:Benzo(a)pyrene; D003367:Cotinine