Serial Review : Role of Reactive Oxygen and Nitrogen Species ( ROS / RNS ) in Lung Injury and Diseases

Exposure to asbestos causes cellular damage, leading to asbestosis, bronchogenic carcinoma, and mesothelioma in humans. The pathogenesis of asbestos-related diseases is complicated and still poorly understood. Studies on animal models and cell cultures have indicated that asbestos fibers generate reactive oxygen and nitrogen species (ROS/RNS) and cause oxidation and/or nitrosylation of proteins and DNA. The ionic state of iron and its ability to be mobilized determine the oxidant-inducing potential of pathogenic iron-containing asbestos types. In addition to their capacity to damage macromolecules, oxidants play important roles in the initiation of numerous signal transduction pathways that are linked to apoptosis, inflammation, and proliferation. There is strong evidence supporting the premise that oxidants contribute to asbestos-induced lung injury; thus, strategies for reducing oxidant stress to pulmonary cells may attenuate the deleterious effects of asbestos. © 2003 Elsevier Inc. Keywords—Asbestos fibers, Cell injury, Mesothelioma, ROS, RNS, Fibrosis, Lung cancers, Free radicals This article is part of a series of reviews on “Role of Reactive Oxygen and Nitrogen Species (ROS/RNS) in Lung Injury and Diseases. ” The full list of papers may be found on the homepage of the journal. Arti Shukla received her Ph.D in Biochemistry from the Banaras Hindu University (Varanasi, India) and did her postdoctoral training at the University of Michigan (Ann Arbor, MI, USA). Presently, she is a Research Assistant Professor in the Department of Pathology at the University of Vermont (Burlington, VT, USA). Her research interest lies in studying cell signaling mechanisms in asbestos-induced lung injury. Mary Gulumian received her Ph.D. from the University of Witwatersrand (Johannesburg, South Africa), where she is presently an Honorary Lecturer in the Department of Hematology and Molecular Medicine. She is also Chief Specialist Scientist and Head of the Toxicology and Biochemistry Research at the National Center for Occupational Health, where she is engaged in research on surface activity of asbestos fibers. Tom K. Hei received his Ph.D. in Experimental Pathology from Case Western Reserve University (Cleveland, OH, USA). He is currently a Professor of Radiation Oncology and a Professor of Environmental Health Sciences at Columbia University (New York, NY, USA). His research interest focuses on the mechanisms of lung and breast cancers, particularly those pertaining to radiation and environmental origins. David Kamp received his M.D. degree from Wayne State University Medical School (Detroit, MI, USA). He is currently an Associate Professor of Medicine at Northwestern University Medical School (Evanston, IL, USA) and Chief of the Pulmonary Section at VAChicago: Lakeside. His research interests focus on exploring the molecular mechanisms underlying asbestos-induced epithelial cell injury. Qamar Rahman received her Ph.D. in the area of Fiber Toxicology from Agra University Agra. She is currently Deputy Director and Chief of Health Risk Assessment and Inhalation Toxicology Areas and Head of the Fiber Toxicology Division at the Industrial Toxicology Research Center (Lucknow, India). She is also Adjunct Professor at Hamdard University in Delhi, India. Her research interest is the toxicity of asbestos at the molecular level both in experimental models as well as in exposed human populations. Brooke T. Mossman received her Ph.D. in the Cell Biology Program at the University of Vermont College of Medicine (Burlington, VT, USA). She is currently a Professor of Pathology and Director of the Environmental Pathology Program at the University of Vermont, where she is pursuing research on mechanisms of asbestos-induced cell signaling and gene expression. Address correspondence to: Dr. Brooke T. Mossman, University of Vermont College of Medicine, Department of Pathology, 89 Beaumont Avenue, Burlington, VT 05405, USA; Tel: (802) 656-0382; Fax: (802) 656-8892; E-Mail: brooke.mossman@uvm.edu. Free Radical Biology & Medicine, Vol. 34, No. 9, pp. 1117–1129, 2003 Copyright © 2003 Elsevier Inc. Printed in the USA. All rights reserved 0891-5849/03/$–see front matter doi:10.1016/S0891-5849(03)00060-1