The effect of iron on the biological activities of erionite and mordenite.

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 fiber surfaces is critical for inducing genotoxic damage.