Metabolic activation and detoxication of environmental chemicals that produce tissue selective cytotoxicity, particularly of the lung; mechanisms for cellular degeneration, especially the role of reactive metabolites; use of DNA arrays and proteomics in toxicology. Our work focuses on understanding the underlying biochemical and metabolic mechanisms for the pulmonary toxicity associated with agents which undergo metabolism to reactive electrophilic metabolites by the cytochrome P450 monooxygenases. The overarching goal of this work is to understand the mechanisms in rodent models so that these can be probed in either non human primates or in humans with either appropriate biomarkers or in vitro studies. We are utilizing proteomics to identify protein targets for reactive metabolites, are examining the redox status of the lung proteome in response to some of these agents and are applying genome wide transcriptome analysis to determine the precise reactions of tissue to injury. Overall, this work is intended o aid in the assessment of risk to human populations for the chemicals under study and should identify enzyme pathways where genetic polymorphisms could lead to altered susceptibility of human populations.
Visit Dr. Buckpitt's website: http://faculty.vetmed.ucdavis.edu/faculty/arbuckpitt/