The metabolic basis of benzene induced myelotoxicity remains poorly understood. We have examined bioactivation of the secondary phenolic metabolites of benzene in the target organ of benzene's toxicity - the bone marrow. We propose to extend this work to examine quantitative and enzymological aspects of bioactivation in specific cell types - unpurified white bone marrow cells, macrophages, neutrophilic cells and stromal fibroblasts. We will examine enzymology responsible for activation and deactivation of phenolic metabolites of benzene and trans muconaldehyde in specific cell types. We also propose to determine whether metabolites of benzene alter prostaglandin production in specific cells since eiconsanoids are important regulators of hemopoiesis. Interactions between phenolic metabolites of benzene will be examined in specific cells. The formulation of DNA adducts from phenolic metabolites of benzene and trans muconaldehyde will be examined in specific cells using HPLC and 32P methodology. This work should greatly increase our understanding of the metabolic mechanisms underlying benzene-induced myelotoxicity.
NIH ExPorter
NIH ExPorter