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 induce genotoxic effects by the inflammation and by inherent primary and/or secondary genotoxic properties. Inflammatory cells and stimulated alveolar macrophages are the main sources of reactive oxygen species (ROS); additionally, -OH radicals generated at the particle surface could be effective in this kind. ROS in the lung is both toxic and mutagenic in generating different types of DNA alterations, especially 8-oxoGua. The development of analytical methods to detect background damage to DNA was critical to the appreciation of the importance of endogenous oxidative damage in carcinogenesis and the importance of potent defense systems of the DNA. We developed a technique (ICA) permitting determination of the content of 8-oxoGua in single cells compromising antioxidative capacity and DNA repair activity. This methodology 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 genotoxic 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 linked with different thresholds. These doses are dearly above inflammatory and fibroblastic effects. The data support the thesis that quartz fine dust in higher doses possibly exerts secondary genotoxic effects and that different quartz species have different genotoxic potential.