Primary and secondary genotoxicity of quartz fine dust - Concept for the quantitative risk assessment of the carcinogenic potential of crystalline silica

The research project is focused on the potential of quartz fine dust to ind uce genotoxic effects by the inflammation and by inherent primary and/or se condary genotoxic properties. Inflammatory cells and stimulated alveolar ma crophages are the main sources of reactive oxygen species (ROS); additional ly, -OH radicals generated at the particle Sur ace co Id be effective in th is kind. ROS in the lung is both toxic and mutagenic in generating differen t types of DNA alterations, especially 8-oxoGua. The development of analyti cal methods to detect background damage to DNA was critical to the apprecia tion of the importance of endogenous oxidative damage in carcinogenesis and the importance of potent defense systems of the DNA. We developed a techni que (ICA) permitting determination of the content of 8-oxoGuo in single cel ls compromising antioxidative capacity and DNA repair activity. This method ology is used for molecular dosimetry and for quantitative risk assessment. The effects of different doses of quartz DQ12 were tested in the rat model for various parameter of pathogenicity (BAL-PMN, TNF PG/PI) and for genoto xic effects (8-oxoGua, p53 mut). Significant genotoxic effects of DQ12 were observed at a threshold dose of 1.0 mg. Different species of quartz are li nked with different thresholds. These doses ore clearly above inflammatory and fibroblastic effects. The data support the thesis that quartz fine dust in higher doses possibly exerts secondary genotoxic effects and that diffe rent quartz species have different genotoxic potential.