The influence of occupational exposure to PAHs on the blood plasma levels of p53 and p21WAF1 proteins.
Polycyclic aromatic hydrocarbons (PAHs) are the main source of carcinogenic risk among coke-oven workers. p53 is a tumor suppressor protein that is induced after DNA damage. It regulates the transcription of genes responsible for cell cycle arrest and apoptosis. p21(WAF1) protein is a downstream effector of p53; it induces cell cycle arrest either in the G(1), S, or G(2) phases. It has been shown that carcinogenic PAHs are able to induce the expression of both p53 and p21(WAF1) proteins in vitro. The purpose of the present study was to evaluate the effect of occupational exposure to carcinogenic PAHs on the level of p53 and p21(WAF1) proteins in blood plasma. The exposed group consisted of 66 coke-oven workers (males, average age 41 years, 42% smokers, 58% nonsmokers); the control group consisted of 49 machine workers (males, average age 49 years, 51% smokers, 49% nonsmokers). No difference in the plasma levels of either p53 (using anti-p53 antibody identifying both the mutated and the wild-type form of the protein) or p21(WAF1) protein was found between the exposed and control groups. Smoking had no effect on the levels of either protein in any of the analyzed groups. After stratification of all the subjects into groups according to their exposure to carcinogenic PAHs, a significantly higher level of p53 was found in the group exposed to carcinogenic PAHs <1 microg/m(3) as compared with the group exposed to carcinogenic PAHs >1 microg/m(3). A similar trend was observed for p21(WAF1) protein, even if no correlation between the levels of both proteins was detected. In the overall study a negative correlation between the levels of p53 protein and personal exposure to carcinogenic PAHs was found. These results did not support the expected response. The use of p53 as well as p21(WAF1) protein plasma levels as biomarkers of carcinogenic PAHs exposure requires further studies.
Rössner
Pavel
P
Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, Regional Institute of Hygiene of Central Bohemia, Vídenská 1083, 142 20 Prague 4, Czech Republic. rossner@biomed.cas.cz
Binková
Blanka
B
Srám
Radim J
RJ
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002273:Carcinogens / Q000633:toxicity; D016022:Case-Control Studies; D003077:Coke / Q000633:toxicity; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000097:blood*
D015415:Biomarkers; C493956:CDKN1A protein, human; D002273:Carcinogens; D003077:Coke; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011084:Polycyclic Aromatic Hydrocarbons; D016159:Tumor Suppressor Protein p53