Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases

doi:10.1016/S0891-5849(03)00060-1

Free Radical Biology and Medicine

Volume 34, Issue 9, 1 May 2003, Pages 1117-1129

https://doi.org/10.1016/S0891-5849(03)00060-1 Get rights and content

Abstract

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.

Introduction

Asbestos is a group of naturally occurring mineral fibers (defined as having a ≥3:1 length to diameter ratio) that are associated with the development of both malignant (lung cancers, mesothelioma) and nonmalignant (asbestosis) diseases in the lung and pleura 1, 2, 3. The role of surface activity on the toxicity and carcinogenicity of asbestos fibers has been well documented [4]. A main factor in determining the surface and biological reactivity of asbestos fibers is their ability to participate in redox reactions that generate free radicals. Free radicals generated from asbestos fibers and/or damage by fibers are linked to cell signaling, inflammation, and a plethora of other responses (mutagenesis, proliferation, etc.) associated with the pathogenesis of asbestos-associated diseases. In this review, we first discuss the types and features of asbestos fibers, determining their surface reactivity. We then review the role of reactive oxygen and nitrogen species (ROS/RNS) in asbestos-associated cell responses and their relationship to the induction of disease.

Section snippets

Surface activity and types of asbestos

Properties such as chemical composition, atomic structure, microtopography, surface charge, and dissolution and adsorption of ions and macromolecules have been associated with the biological effects of asbestos fibers. These surface characteristics are affected by the mechanical and thermal history of the fibers, by their chemical treatment, and also by the presence of impurities in the mineral. Due to this changeability in surface characteristics, the surface activity of asbestos fibers may

Surface adsorptive and active sites and the ability of asbestos to generate oh^• by reducing oxygen and by participating in a fenton-type reaction

Similar adsorptive sites occur on both chrysotile and crocidolite asbestos fibers 10, 11. On chrysotile, abundant basic hydroxyl sites exist on the outer layer of the octahedral sheet with minor concentrations of acceptor acidic sites. On crocidolite, surface adsorptive sites are of similar Lewis base character. Surface active sites reducing O₂ and catalyzing the decomposition of H₂O₂ are more related to the presence and ionic state of iron 12, 13, 14.

The ability of asbestos fibers to generate

The role of iron in asbestos fibers in the generation of ^•oh

The nature of the aforementioned free radical-generating surface sites on asbestos fibers is not yet clear. However, iron present in asbestos fibers is thought to be an important factor in the generation of ^•OH produced from the reduction of O₂ or from the decomposition of H₂O₂. Studies have shown that the ability of asbestos fibers to elicit these effects is not related to total iron content, suggesting the presence of specific iron active sites that exist at the surface and become active in

Ros/rns in cell responses to asbestos

Asbestos fibers have been studied for decades in numerous in vitro assays to determine their mechanisms of cytotoxicity, DNA damage, and mutagenesis. The prevention of asbestos-induced cytotoxicity and protooncogene induction by antioxidants 3, 32, 33 and the ability of longer, more pathogenic asbestos fibers to cause production of oxidants by frustrated phagocytosis 34, 35 provides compelling evidence that oxidants contribute to asbestos-induced cell injury.

Evidence for oxidants in asbestos-induced inflammatory responses and disease

Although lung fluids have a battery of antioxidants including ceruloplasmin and extracellular SOD, the lung environment may also promote formation of ROS from asbestos. For example, surfactant-coated crocidolite fibers released more iron than native fibers at both pH 4.5 and 7.2, an observation indicating that in vivo lung lining fluid coats native fibers and, therefore, affects the fiber surface chemistry and reactivity [74]. Also, it has been demonstrated that intratracheal instillation of

Rns and pulmonary toxicity

In addition to ROS-induced effects, pulmonary toxicity by asbestos may be modulated by nitric oxide (NO^•) or peroxynitrite (ONOO⁻) [78]. Use of a nitric oxide synthase (NOS) inhibitor prevented asbestos-induced formation of 8-OHdG, supporting a role for NO^• in asbestos-induced oxidation [79]. NOS activity in rat lung and NO^• synthesis in alveolar macrophages increased after instillation of asbestos into the trachea [80]. It has been suggested that small numbers of crocidolite fibers translocate

Role of ros and rns in asbestos-induced cell signaling

After interaction with cells, asbestos fibers triggered numerous signaling cascades involving mitogen-activated protein kinases (MAPK) and nuclear factor κB (NF-κB) 87, 88. Activation of transcription factors such as NF-κB and activator protein-1 (AP-1) may be linked to increases in early response genes (i.e., jun and fos), which govern proliferation, apoptosis, and inflammatory changes [89]. Recent evidence indicates that asbestos can stimulate gene expression in a variety of cell types via

Conclusions and clinical relevance

Asbestos is a physiologically relevant oxidative stress in lung that has resulted in thousands of deaths from lung cancers, mesotheliomas, and pulmonary fibrosis. The potency of various types of asbestos in human disease was first suggested in the classical epidemiological study by Wagner and colleagues [107], which described a high incidence of mesotheliomas in South African crocidolite miners, some tumors in workers mining amosite, and no tumors in workers mining chrysotile asbestos. Over the

Abbreviations

AEC—alveolar epithelial cells
8-OHdG—8-hydroxydeoxyguanosine
GSH—glutathione
MAPK—mitogen-activated protein kinase
NF-κB—nuclear factor κB
NFAT—nuclear factor of activated T cells (NFAT)
NO^•—nitric oxide
NOS—nitric oxide synthase
ONOO⁻—peroxynitrite
RNS—reactive nitrogen species
ROS—reactive oxygen species
TdT—terminal deoxynucleotidyl transferase
TiO₂—titanium dioxide
TNF-α—tumor necrosis factor-α

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.

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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 VA-Chicago: 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.

^☆

Guest Editor: Brooke T. Mossman

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.

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Serial review: role of reactive oxygen and nitrogen species (ROS/XRNS) in lung injury and diseasesMultiple roles of oxidants in the pathogenesis of asbestos-induced diseases☆

Abstract

Introduction

Section snippets

Surface activity and types of asbestos

Surface adsorptive and active sites and the ability of asbestos to generate oh• by reducing oxygen and by participating in a fenton-type reaction

The role of iron in asbestos fibers in the generation of •oh

Ros/rns in cell responses to asbestos

Evidence for oxidants in asbestos-induced inflammatory responses and disease

Rns and pulmonary toxicity

Role of ros and rns in asbestos-induced cell signaling

Conclusions and clinical relevance

Abbreviations

J. Inorg. Biochem

Environ. Res

Arch. Biochem. Biophys

Environ. Res

Chem. Biol. Interact

Environ. Res

Arch. Biochem. Biophys

Arch. Biochem. Biophys

J. Inorg. Biochem

Arch. Biochem. Biophys

Arch. Biochem. Biophys

J. Immunol. Methods

J. Lab. Clin. Med

Free Radic. Biol. Med

J. Biol. Chem

Free Radic. Biol. Med

Mutat. Res

Free Radic. Biol. Med

Am. J. Pathol

Ann. Occup. Hyg

Free Radic. Biol. Med

Arch. Biochem. Biophys

Free Radic. Biol. Med

Free Radic. Biol. Med

Toxicol. Lett

Asbestos-related disease

N. Engl. J. Med

Asbestosscientific developments and implications for public policy

Science

Mechanisms of carcinogenesis and clinical features of asbestos-associated cancers

Cancer Invest

Health effects of mineral dusts

Mineralogy of amphiboles and 11 layer silicates

Rev. Mineral

Mössbauer spectroscopic studies on three different types of crocidolite fibres

S. A. J. Sci

Can microwave radiation at high temperatures reduce the toxicity of fibrous crocidolite asbestos?

Environ. Health Perspect

Chemical applications of the Mössbauer effect. Part 2. Oxidation states of iron in crocidolite and amosite

Trans. Faraday Soc

Study of electron donor and acceptor sites on the surface of asbestos fibres (Etude des sites donneurs et accepteurs d’un electron en surface des amiantes)

J. Chimie Physique

Production of hydroxyl radicals by iron solid compounds

Toxicol. Environ. Chem

Production of oxygen radicals by the reduction of oxygen arising from the surface activity of mineral fibres

The role of iron in the redox surface activity of fibres. Relation to carcinogenicity

Oxygen consumption, lipid peroxidation, and mineral fibres

Effect of microwave radiation on surface charge, surface sites, and ionic state of iron, and the activity of crocidolite asbestos fibres

Hyperfine Interact

Detoxified crocidolite exhibits reduced radical generation, which could explain its lower toxicity: ESR and Mössbauer studies

An investigation of the mechanism of detoxification in asbestos

Hyperfine Interact

Free radical generation in the toxicity of inhaled mineral particlesthe role of iron speciation at the surface of asbestos and silica

Redox. Rep

Parameters which determine the activity of the transition metal iron in crocidolite asbestosESR, Mössbauer spectroscopic, and iron mobilization studies

S. A. J. Sci

Iron mobilization from asbestos by chelators and ascorbic acid

Arch. Biochem. Biophys

Glutathione redox system in oxidative lung injury

Crit. Rev. Toxicol

The molecular basis of asbestos-induced lung injury

Thorax

Generation of superoxide (O2−•) from alveolar macrophages exposed to asbestiform and nonfibrous particles

Cancer Res

Role of reactive oxygen metabolites in crocidolite asbestos toxicity to mouse macrophages

Cancer Res

Iron-dependent formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA102 induced by crocidolite

Serial review: role of reactive oxygen and nitrogen species (ROS/XRNS) in lung injury and diseases
Multiple roles of oxidants in the pathogenesis of asbestos-induced diseases☆

Surface adsorptive and active sites and the ability of asbestos to generate oh^• by reducing oxygen and by participating in a fenton-type reaction

The role of iron in asbestos fibers in the generation of ^•oh

Generation of superoxide (O₂⁻^•) from alveolar macrophages exposed to asbestiform and nonfibrous particles