Role of iron in the reactivity of mineral fibers

Environmental and/or occupational exposure to minerals, metals, and fibers can cause lung diseases that may develop years after exposure to the agents. The presence of toxic fibers such as asbestos in the environment plus the continuing development of new mineral or vitreous fibers requires a better understanding of the specific physical and chemical features of fibers/particles responsible for bioactivity. Toward that goal, we have tested aluminosilicate zeolites to establish biological and chemical structure-function correlations. Zeolites have known crystal structure, are subject to experimental manipulation, and can be synthesized and controlled to produce particles of selected size and shape. Naturally occurring zeolites include forms whose biological activity is reported to range from highly pathogenic (erionite) to essentially benign (mordenite). Thus, we used naturally occurring erionite and mordenite as well as an extensively studied synthetic zeolite based on faujasite (zeolite Y). Bioactivity was evaluated using lung macrophages of rat origin (cell line NR8383). Our objective was to quantitatively determine the biological response upon interaction of the test particulates/fibers with lung macrophages and to evaluate the efficacy of surface iron on the zeolites to promote the Fenton reaction. The biological assessment included measurement of the reactive oxygen species by flow cytometry and chemiluminescence techniques upon phagocytosis of the minerals. The chemical assessment included measuring the hydroxyl radicals generated from hydrogen peroxide by iron bound to the zeolite particles and fibers (Fenton reaction). Chromatography as well as absorption spectroscopy were used to quantitate the hydroxyl radicals. We found that upon exposure to the same mass of a specific type of particulate, the oxidative burst increased with decreasing particle size, but remained relatively independent of zeolite composition. On the other hand, the Fenton reaction depended on the type of zeolite, suggesting that the surface structure of the zeolite plays an important role.

Section: Role Of Zeolite Surface Structure In Fenton Chemistrysupporting

confidence: 71%

Section: Correlation Of Biological and Chemical Reactivitiessupporting

confidence: 38%

Section: Correlation Of Biological and Chemical Reactivitiesmentioning

confidence: 99%

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Analysis of the biological and chemical reactivity of zeolite-based aluminosilicate fibers and particulates.

Fach

Waldman

Williams

et al. 2002

“…Not all iron was active, in agreement with a large number of cell-free tests indicating that only a small fraction of total iron present is capable of generating ROS (31,43,50 (44,53). Singlestrand DNA damage correlates with iron that may be mobilized from asbestos by low molecular weight chelators, which suggests a direct relationship between free radical generation and mobilized iron (44,53 The iron involved in the reactionoriginating ROS may be in the chemical composition of the fiber (amphibole asbestos) or present as an impurity (chrysotile and glass fibers) (31,(48)(49)(50)(51)(52). There is evidence that endogenous iron is deposited on the fiber surface from macrophages or other cells (57) that might also become active.…”

Section: Transition Metals and Free Radical Releasementioning

confidence: 60%

Surface reactivity in the pathogenic response to particulates.

Fubini

1997

122

100

The peculiar characteristics of dust toxicity are discussed in relation to the processes taking place at the particle-biological medium interface. Because of surface reactivity, toxicity of solids is not merely predictable from chemical composition and molecular structure, as with water soluble compounds. With particles having the same bulk composition, micromorphology (the thermal and mechanical history of dust and adsorption from the environment) determines the kind and abundance of active surface sites, thus modulating reactivity toward cells and tissues. The quantitative evaluation of doses is discussed in comparisons of dose-response relationships obtained with different materials. Responses related to the surface of the particle are better compared on a per-unit surface than per-unit weight basis. The role of micromorphology, hydrophilicity, and reactive surface cations in determining the pathogenicity of inhaled particles is described with reference to silica and asbestos toxicity. Heating crystalline silica decreases hydrophilicity, with consequent modifications in membranolytic potential, retention, and transport. Transition metal ions exposed at the surface generate free radicals in aqueous suspensions. Continuous redox cycling of iron, with consequent activation-reactivation of the surface sites releasing free radicals, could account for the long-term pathogenicity caused by the inhalation of iron-containing fibers. In various pathogenicities caused by mixed dusts, the contact between components modifies toxicity. Hard metal lung disease is caused by exposure to mixtures of metals and carbides, typically cobalt (Co) and tungsten carbide (WC), but not to single components. Toxicity stems from reactive oxygen species generation in a mechanism involving both Co metal and WC in mutual contact. A relationship between the extent of water adsorption and biopersistence is proposed for vitreous fibers. Modifications of the surface taking place in vivo are described for ferruginous bodies and for the progressive comminution of chrysotile asbestos fibers. Environ Health Perspect 1 05(Suppl 5): 1013-1020 (1997)

“…The most widely used in vitro gene mutation assays are based on reverse mutation in Salmonella typhimurium (21) (40). The state of iron reacting in these processes strongly influences the effects: reduced iron and mobilizable iron are believed to be important in the production of ROS (44)(45)(46). To be efficient, Fe(III) must be chelated in solution to permit its reduction (47).…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of fiber-induced genotoxicity.

Jaurand

1997

117

The mechanisms of particle-induced genotoxicity have been investigated mainly with asbestos fibers. The results are summarized and discussed in this paper. DNA damage can be produced by oxidoreduction processes generated by fibers. The extent of damage yield depends on experimental conditions: if iron is present, either on fibers or in the medium, damage is increased. However, iron reactivity does not explain all the results obtained in cell-free systems, as breakage of plasmid DNA was not directly associated with the amount of iron released by the fibers. The proximity of DNA to the site of generation of reactive oxygen species (ROS) is important because these species have an extremely short half-life. Damage to cellular DNA can be produced by oxidoreduction processes that originate from cells during phagocytosis. Secondary molecules that are more stable than ROS are probably involved in DNA damage. Oxidoreduction reactions originating from cells can induce mutations. Genotoxicity is also demonstrated by chromosomal damage associated with impaired mitosis, as evidenced by chromosome missegregation, spindle changes, alteration of cell cycle progression, formation of aneuploid and polyploid cells, and nuclear disruption. In some of these processes, the particle state and fiber dimensions are considered important parameters in the generation of genotoxic effects.