Exposure to complex mixtures in food, air and water is common. Information to describe the pharmacokinetics and toxicity of mixtures is very limited. The objective of Project 2 of the Texas A&M Superfund Basic Research Program is to investigate the mechanisms of complex mixture genotoxicity. The proposed study will focus on two common environmental mixtures, polycyclic aromatic hydrocarbons (PAHs), and mixtures of PAHs and halogenated aromatic hydrocarbons (HAHs). These chemicals are common components of mixtures found at petroleum refineries, manufactured gas plants and wood preserving plants. This Project has four specific aims including: (1) to fractionate and chemically characterize a minimum of three complex PAH and PAH:HAH mixtures; (2) to investigate the in vitro and in vivo genotoxicity and epigenetic toxicity of a series of model compounds and complex mixtures of PAHs and PAHs:HAHs; (3) to compare the frequency of DNA adducts and tumors in sensitive and resistant animal models; and (4) to monitor biomarkers of exposure and effect in rodents and humans exposed to complex mixtures. The project will investigate the chemical composition of model compounds and mixtures, as well as their ability to cause genotoxic or epigenetic damage in cell culture or animal models. Ultimately, the study proposes to monitor biomarkers in ecological and human populations exposed to mixtures that are similar in composition to those studied in the laboratory. The results of the project will improve our ability to identify the major genotoxic components of mixtures. Research results will also identify appropriate biomarkers that may be used to evaluate exposure to genotoxic chemicals.
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