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[Cancer Research 61, 778-784, January 15, 2001]
© 2001 American Association for Cancer Research

Regular Articles

Nitrated and Oxidized Plasma Proteins in Smokers and Lung Cancer Patients1

Brigitte Pignatelli, Chun-Qi Li2, Paolo Boffetta, Qiping Chen, Wolfgang Ahrens, Fredrik Nyberg, Anush Mukeria, Irene Bruske-Hohlfeld, Cristina Fortes, Vali Constantinescu, Harry Ischiropoulos and Hiroshi Ohshima3

International Agency for Research on Cancer, F-69372 Lyon Cedex 08, France [B. P., C-Q. L., P. B., H. O.]; The Stokes Research Institute and Department of Pediatrics, Neonatology Division, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19140 [Q. C., H. I.]; Bremen Institute for Prevention Research and Social Medicine (BIPS), 28199 Bremen, Germany [W. A.]; Institute of Environmental Medicine, Karolinska Institute, 17177 Stockholm, Sweden [F. N.]; Institute of Carcinogenesis, 115478 Moscow, Russia [A. M.]; National Research Center for Environment and Health (GSF), 85758 Munich, Germany [I. B-H.]; Regional Epidemiological Unit, 00198 Rome, Italy [C. F.]; and National Institute of Public Health, 76256 Bucharest, Romania [V. C.]

Cigarette smoking is a cause of lung cancer and other respiratory diseases. Oxidants either present in cigarette smoke and/or formed in the lung of smokers may trigger oxidative and nitrative damage to DNA and cellular components, contributing to carcinogenesis. We have used immunodot and Western blot analyses to measure nitrated (nitrotyrosine-containing) and oxidized (carbonyl-containing) proteins in plasma samples collected from 52 lung cancer patients and 43 control subjects (heavy and light smokers, nonsmokers with or without exposure to environmental tobacco smoke). The levels of nitrated proteins were significantly higher in lung cancer patients than in controls (P = 0.003). On the other hand, the levels of oxidized proteins were significantly higher in smokers than in nonsmokers (P < 0.001). Western-blot analyses showed the presence of two to five nitrated proteins and one oxidized protein. Using immunoprecipitation and Western-blot analyses with eight different antibodies against human plasma proteins, we identified fibrinogen, transferrin, plasminogen, and ceruloplasmin as nitrated proteins and fibrinogen as the only oxidized protein present in human plasma of lung cancer patients and smokers. Our results indicate that cigarette smoking increases oxidative stress and that during lung cancer development, formation of reactive nitrogen species results in nitration and oxidation of plasma proteins.




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