Influence of occupational and environmental metal exposure on DNA-damage and DNA-repair capacity: Comparison of established and new biomarkers as to their predictivity for cancer development

Status:

completed 06/2010

Aims:

For carcinogenic substances including carcinogenic metal compounds the new legislation requires health-based occupational exposure limit values. An important prerequisite is the establishment of reliable dose-response relationships for the most sensitive endpoints including those related to genotoxicity. Furthermore, when threshold values are proposed, the mechanisms of action of the respective substances have to be considered. Hence, the aim of this study was to apply newly established biomarkers for genotoxicity and to investigate their associations with occupationally or environmentally caused metal exposure.

Activities/Methods:

In the cross sectional study WELDOX, 243 welders from 23 different companies were examined with respect to their individual welding fume and metal exposure. Three newly developed biomarkers for genotoxicity were in the focus of this study. As a measure for oxidative DNA damage, the number of FPG-sensitive sites per 106 base pairs and as a measure of DNA repair capacity the individual PARP activities and incisions capacities were determined.

Results:

From this joint project it can be concluded that the methods used here are suitable to quantify potential genotoxic effects caused by occupational or environmental metal exposure. The application of the newly developed biomarkers could indeed help to establish health-based exposure limit values for carcinogenic metal compounds in the future.

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