mordenite and erionite

Respirable mineral fibers, such as asbestos, are known to cause pleural mesothelioma, pulmonary fibrosis, and bronchial carcinoma, often years after exposure. Erionite and mordenite, two mineral aluminosilicates (zeolites) with different toxicities, can be used as models to help understand asbestos toxicity. Erionite is carcinogenic, while mordenite is relatively benign. No iron is typically present in erionite or mordenite, but because of their ion-exchange properties they can acquire iron after inhalation. The iron is typically in the Fe(III) form and will need to be reduced prior to any Fenton activity. Lung lining fluid contains antioxidants, such as glutathione (GSH) and ascorbic acid (AA), which can reduce Fe(III) to Fe(II). In this study, we have compared the Fenton reactivity of Fe(III)-exchanged erionite and mordenite after treatment with antioxidants. The Fenton assay involved the reaction of hydroxyl radicals with dimethyl sulfoxide. Fenton reactivity was most marked with AA followed by GSH, and hydrogen peroxide also exhibited minor reactivity. Erionite generated an order of magnitude greater hydroxyl radicals than mordenite, normalized to the surface iron content, providing support for the hypothesis that the iron coordination at the mineral surface plays a significant role in bioactivity.

Topics: Aluminum Silicates; Asbestos; Hydrogen Peroxide; Hydroxyl Radical; Iron; Lung Neoplasms; Mesothelioma; Oxidation-Reduction; Pulmonary Fibrosis; Zeolites

Epidemiological data has demonstrated that environmental and/or occupational exposure to mineral particulates may result in the development of pulmonary fibrosis, bronchogenic carcinoma and malignant mesothelioma many years following exposure. It has been suggested that the genotoxic effects of fibrous particulates, such as asbestos, is due in part to the generation of reactive oxygen species (ROS) from iron associated with the particulates. However, the molecular mechanisms by which mineral particulates induce ROS that results in genotoxic damage remains unclear. The naturally occurring zeolites, erionite and mordenite share several physiochemical properties but they elicit very different biological responses, with erionite, a fibrous particulate, being highly toxic, and mordenite, a nonfibrous particulate, being relatively benign. We are using these natural zeolites as a model system to determine what physicochemical properties of these zeolites are responsible for their biological response(s) and to evaluate the parameters that influence these responses. The purpose of the present study was to determine the mutagenic potential of erionite and mordenite and to determine whether this mutagenic potential was modulated by iron. The results of this study using the Chinese hamster ovary cell line AS52 demonstrated that erionite was more cytotoxic than mordenite. However, the cytotoxicity of both zeolites was increased in the presence of physiological concentrations of ferrous chloride. Ferrous ions (5-20 microM) significantly (p<0.001) increased the cytotoxicity of mordenite, but only at the highest concentration (16 microg/cm(2)) of mordenite tested. Conversely, only the highest concentration (20 microM) of ferrous ion significantly (p<0.001) increased the cytotoxicity of erionite, but this enhanced cytotoxicity occurred over a wider concentration range (6-16 microg/cm(2)) of erionite. Mordenite was not mutagenic at any of the concentrations tested, and the mutagenic potential of mordenite was not enhanced by the addition of ferrous ion. Conversely, erionite was mutagenic in a dose-response manner at concentrations greater than 6 microg/cm(2) and the mutagenic potential of erionite was significantly enhanced by the addition of ferrous ions. These results suggest that while the cytotoxicity of mordenite and erionite may be related to the ability of these fibers to transport iron into a cell, the different coordination state of iron associated with the two fi

Topics: Aluminum Silicates; Animals; CHO Cells; Cricetinae; DNA Damage; Dose-Response Relationship, Drug; Drug Interactions; Iron; Mutagenicity Tests; Zeolites

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.

Topics: Aluminum Silicates; Animals; Cell Line; Chromatography; Hydrogen Peroxide; Hydroxyl Radical; Iron; Macrophages, Alveolar; Oxidants; Rats; Structure-Activity Relationship; Zeolites