The major goal of this project is to determine the genetic toxicity of complex chemical mixtures present in field extracts from wood preserving and oily waste sites as an indicator of their potential carcinogenicity. Field extracts will be tested in a mouse model and by a novel in vitro system for the induction of DNA damage (covalent DNA adducts), which will be assessed by the 32P-postlabeling assay. The investigators propose to (1) produce extract- and tissue-specific PAH- DNA adduct profiles and levels as genotoxic endpoints, (2) identify the sources of major PAH-DNA adducts induced by field extracts, (3) show whether polychlorinated phenols induce oxidative stress-associated bulky DNA lesions, (4) determine the relationships between genotoxic potencies of field extracts and tumor initiating activities, (5) assess possible synergistic or antagonistic interactions between chemicals in field extracts in vivo, (6) examine whether field extracts elicit reductions of hepatic I-compound levels in the mouse model, and (7) test whether, in the absence of metabolic activation, aqueous extracts of field samples induce extract-specific DNA adduct profiles and levels in vitro and whether this property represents an indicator of genotoxicity of aqueous dumpsite effluents. These studies are designed to provide qualitative and quantitative data on the toxicity of wood preserving and oily waste sites to the genetic material of a cell.
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