Inhaled crocidolite mutagenicity in lung DNA.

Rihn, Bertrand; Coulais, Catherine; Kauffer, E.; Bottin, M.C.; Martin, Patrick; Yvon, François; Vigneron, J. C.; Binet, Stéphane; Monhoven, Nathalie; Steiblen, Guy; Keith, Gérard

doi:10.1289/ehp.00108341

Cited by 33 publications

(26 citation statements)

References 34 publications

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“…This observation may be due to consumption of O 2 À by the Fenton's reaction with iron at the surface of CR fiber. Hydroxyl radical formed by iron-catalyzed Fenton's reaction is highly reactive and induces DNA damage (Jackson 1994); therefore, generated AE OH may be implicated in mutagenicity of CR as shown by Rihn et al (2000).…”

Section: Discussionmentioning

confidence: 99%

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes

et al. 2004

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The purpose of this study was to investigate the effects of pneumoconiogenic particles, such as asbestos, on nitrosothiol formation in macrophages. In addition, the effects of man-made mineral fibers (MMMFs) were also evaluated, because they have come into heavy use as substitutes for asbestos. RAW264.7 cells and J774 cells of murine macrophage cell lines were cultured with chrysotile B (CH) asbestos, crocidolite (CR) asbestos, or MMMFs comprised of glass wool (GW), rock wool (RW), or ceramic (RF1). All of these fibers significantly increased nitric oxide (NO) production in the culture with macrophages. Chrysotile B, CR, and GW significantly decreased the level of reduced glutathione (GSH) in RAW264.7 cells. S-nitrosothiol (RS-NO) formation was increased by both types of cells on exposure to every fiber. A large portion of this increased RS-NO may be in the form of S-nitrosoglutathione (GS-NO), because GSH is the most abundant thiol substance in the cell. Both CH and GW significantly increased superoxide anion in the media cultured of RAW264.7 cells. These results indicate that macrophages exposed to asbestos or MMMFs are subject to oxidative stress, not only through the generation of reactive oxygen and nitrogen species, but also through decreases in the level of the cellular antioxidant, GSH, by GS-NO formation. The increase of RS-NO in macrophages exposed to asbestos or MMMFs may deserve more attention as the indicator of continuous oxidative stress by NO on cells and tissues, which causes inflammation and involves the development of asbestos-induced diseases.

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Section: Discussionmentioning

confidence: 99%

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes

et al. 2004

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“…Using the TUNEL method, asbestos fibers have been shown to cause DNA strand breaks in the respiratory epithelium of rats (Jung et al, 2000). Asbestos fibers, as well as diesel exhaust particles, have recently also been applied using transgenic rats that have been specifically designed for in vivo mutagenesis testing (Provost et al, 1993;Dycaico et al, 1994;Zeiger, 1998;Sato et al, 2000;Unfried et al, 2000;Rihn et al, 2000).…”

Section: In Vivo Genotoxicity Testingmentioning

confidence: 99%

“…In vivo mutagenicity has also been tested with diesel exhaust particles and asbestos, using transgenic rats (Sato et al, 2000;Unfried et al, 2000;Rihn et al, 2000). Exposure to DEP (4 wk of exposure, 6 mg/m 3 ), was found to cause a significant, nearly fivefold increase in mutant frequency (Sato et al, 2000).…”

Section: Animal Studiesmentioning

confidence: 99%

Mechanisms of Genotoxicity of Particles and Fibers

Schins

2002

Inhalation Toxicology

228

108

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With regard to genotoxicity testing and cancer risk assessment, particles and fibers form a rather specific group among all toxicants. First, the physicochemical behavior of fibrous and nonfibrous particles is usually very different from that of nonparticulate, chemical carcinogens. Reactive oxygen species (ROS) are believed to play a major role in primary genotoxicity of particles, which may derive from their surface properties, the presence of transition metals, intracellular iron mobilization, and lipid peroxidation. Other aspects relevant to primary genotoxicity are particle size, shape, crystallinity (e.g., silica), and solubility, and may also include particle uptake, interaction with cell division machinery (e.g., asbestos), and the presence of mutagens carried with the particle (e.g., diesel exhaust particles, DEP). Excessive and persistent formation of ROS from inflammatory cells is considered as the hallmark of the secondary genotoxicity of nonfibrous and fibrous particles. Since lung inflammation is known to occur and persist only at sufficient particle dose, this secondary pathway is considered to contain a threshold (Greim et al., 2001). Identification of (mechanisms of) particle genotoxicity has been/can be achieved via (1) acellular assays, (2) in vitro tests, (3) in vivo studies, usually in mice or rats, and finally (4) biomarker studies in humans with (occupational) exposure. The significance of acellular assays and biomarker studies for risk assessment is limited, but has provided some mechanistic insights (e.g., in oxidant generating properties of quartz and asbestos) and may also contribute to hazard identification. In vitro studies have lead to identification of primary genotoxic properties of particles, whereas recent in vivo studies provide further support for the correlation between particle-induced lung inflammation and secondary genotoxicity. Proper risk assessment of particles necessitates identification of the relative impact of primary versus secondary genotoxicity in realistic exposure conditions. However, since it is impossible to discern between primary and secondary genotoxicity with current in vivo tests, concomitant in vitro assays are required to determine primary genotoxicity. In vivo tests should ideally be designed using different doses to allow dose-effect analysis for both inflammation and genotoxicity.

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“…Chronic inflammation induced by the persistence of fibers in tissues may play a role in various stages of tumor development. As it was already evidenced in vivo by crocidolite exposure, ROS and RNS result in the oxidation and nitrosylation of protein, DNA, and lipoperoxidative damage of membrane in adjacent parenchymal cells, namely, type II pneumocytes, fibroblasts, and mesothelial cells [43]. Mesothelial cells and lung epithelial cells (e.g., pneumocytes) are also in direct interaction with fibers and therefore involved in fiber-induced lung disease.…”

Section: Mechanisms Of Fiber-induced Lungmentioning

confidence: 94%

“…The functional and morphometric in vitro differences of cell types might explain why the biopersistence of crocidolite fibers is higher in the peritoneal cavity than in the lung. In the latter environment, fibers induced more damages through more active phagocytosis, generation of oxidative stress, and more mutations compared to the deep lung [43,63]. The higher release of O .− 2 from rat AMs compared to hamster AMs was also related to differences in phagocytic activity [49].…”

Section: Svf-induced Reactive Oxygen Species Releasementioning

confidence: 99%

Macrophage Culture as a Suitable Paradigm for Evaluation of Synthetic Vitreous Fibers

Nguea¹,

Reydellet²,

Faou³

et al. 2008

Critical Reviews in Toxicology

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The ultimate goal of toxicologic investigation of synthetic vitreous fibers (SVFs) is to provide essential input for the assessment of human risk to their exposure. Toxicity of mineral fibers is usually evaluated by testing biopersistence in rodent model. However, a cellular model would be much appreciated in order to reduce, refine, and replace animal models. Pulmonary disorders triggered by inhalation of occupational or environmental mineral particulates can be the endpoints of a chronic inflammatory process in which alveolar macrophages (AMs) play a crucial role. Depending on the type of SVF involved, phagocytosis of fiber leads to activation of macrophages, resulting in release of fiber components and potent mediators, such as reactive oxygen or nitrogen species and cytokines. As a matter of fact, macrophages should be the cells of choice since SVF toxicity is the consequence of fibers and alveolar macrophages interaction. Today, monocytes and macrophages culture are firmly established as a paradigm in toxicology when several endpoints are assayed in macrophages: (1) fiber durability, (2) fiber surface changes, (3) oxidative stress and genotoxicity in macrophage, and (4) macrophage cell viability and apoptosis. This article is a review of up-to-date knowledge of in vitro studies involving macrophages, and assesses endpoints of macrophage toxicity with an emphasis on (1) dissolution, (2) scanning electron microscopy analysis, (3) cytotoxicity, and (4) gene expression.

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Inhaled crocidolite mutagenicity in lung DNA.

Cited by 33 publications

References 34 publications

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes

Production of nitric oxide elevates nitrosothiol formation resulting in decreased glutathione in macrophages exposed to asbestos or asbestos substitutes

Mechanisms of Genotoxicity of Particles and Fibers

Macrophage Culture as a Suitable Paradigm for Evaluation of Synthetic Vitreous Fibers

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