Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

摘要

Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos oxon, and iso-OMPA demonstrates that other important targets exist. The goal of this work is to identify non-acetylcholinesterase targets of organophosphorus toxicants. Using mass spectrometry we have identified platelet activating factor acetyl hydrolase as a sensitive target of organophosphorus insecticides in mouse rain extracts. Two additional biomarkers may be fatty acid amide hydrolase and acylpeptide hydrolase. Studies in living mice to test the involvement of these proteins in low level toxicity are beginning. This work is expected to identify new biological markers for low dos exposure to organophosphorus toxicants and to explain the neurologic symptoms of some of our Gulf War veterans.