Graduate Thesis Or Dissertation

Hemoglobin adducts of the organophosphate insecticide azinphos-methyl

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  • Reported here is an investigation to determine if azinphos-methyl (AZM), an organophosphate insecticide, adducts to hemoglobin, and if so, whether the hemoglobin adduct could be used as a quantitative marker of occupational AZM exposure. We hypothesized that AZM, or a metabolite of AZM, binds to hemoglobin in erythrocytes forming an adducted protein. We administered radiolabled AZM to rats and found a stable, dose-dependent association of radioactivity with hemoglobin. The decline in hemoglobin-associated radioactivity followed the expected kinetics of erythrocyte turnover in rats. We examined hemoglobin isolated from these rats by high-pressure liquid chromatography, liquid scintillation counting, and electrospray ionization mass spectrometry. These analyses provided evidence of AZM or an AZM metabolite binding to one of the beta proteins of hemoglobin. In vitro incubation of AZM with hemoglobin in a liver microsome system indicated an AZM adduct to heme. Further research is necessary to fully characterize the adduct and determine whether this biomarker will be useful for monitoring human exposure to AZM.
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