PROTEINS AND DNA--NEW METHODS OF ADDUCT DETECTION

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Description: The overall goals of this part of the research program are to apply molecular approaches to the development of biomarkers of exposure to some key toxic components in the environment of people living in the Aberjona region. These biomarkers will include readily accessible blood proteins and DNA from cells in blood and also protein and DNA from cells in potential target organs. The proposed research is a continuation and amplification of their earlier ongoing research in these same areas. The methods will include the most advanced approaches in mass spectrometry, cryogenic fluorescence spectroscopy, and postlabeling analysis of modified DNA. The contaminants that will be the main focus of the research will be the polycyclic aromatic hydrocarbons (PAH), representing exposure from air and food, and arsenic and chromium, representing exposure from water. Through examination of both serum albumin and histones and DNA they will try to develop both a short- and long- term scale for exposure and damage. The combined uses of 35S postlabeling and laser fluorescence and electrospray mass spectrometry will give unparalleled sensitivity and specificity to the use of biomarkers in epidemiology. Monoclonal antibodies will be added to those already made to give rapid and accurate analysis of oxidatively modified DNA. Experiments will be conducted to test the possibility of interactions between chromium and arsenic. Finally, all developed biomarkers will be employed in exposure studies on people in the Aberjona region.