DNA damages that are not repaired during cell proliferation represent initiating events that may result in neoplasia. Exposure from polycyclic aromatic hydrocarbons (PAHs) from some foods is sufficiently high to permit direct studies of such DNA lesions in humans. This potential health hazard - its modulation by genetic factors, synergists and protective substances - constitutes the main focus for this proposal. The intent is also to provide new methods for assessing oxidative and other types of DNA damage as well as basic knowledge on different DNA repair mechanisms. The impact from exposures via food to PAHs will be studied in women characterized by different ethnicity and life styles from the general population in Poland, Serbia and Italy, as well as in subjects living in two environmental catastrophe zones in Serbia. Arsenic enhances the genotoxic effects of PAHs in model systems, and the proposed investigation of the effects of combined exposures to PAHs and high levels of arsenic in drinking water is unique, as is the assessment of individual DNA repair capacity, which offers a possibility to identify particularly sensitive groups with respect to this type of carcinogens. In humans the utility of various biomarkers derived from model systems, and that are relevant for tumour induction by PAHs, will be directly assessed by monitoring chromosomal and DNA damage in buccal cells and lymphocytes. The comparative studies to be conducted in the mouse on inhibition of PAH-induced genotoxicity by selected plant constituents provide an input to a subsequent investigation in humans. In this study the inhibiting effects of anticarcinogens with respect to DNA damage and chromosomal aberrations induced by exposure to PAHs will be assessed directly in isolated lymphocytes and buccal cells from human volunteers in an intervention cross-over study. In the area of public health, efforts will be made to promote a healthier diet for the general population.
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Funding SchemeSTREP - Specific Targeted Research Project