Five h after administration of35S-malathion (30 μCi) to rats, the amount of total radioactivity and that bound to macromolecules in various tissues were determined. It was found that the amount of bound radioactivity was distributed in the liver > spleen > kidney > lung > brain, while the amount of total radioactivity in the spleen > kidney > liver > lung > brain respectively. In the subcellular fraction, bound radioactivity was predominantly distributed in microsome, and less frequently in nuclei, cell debris, and mitochondria. Small amount was found in supernatant. After rats had been pretreated with phenobarbital, the amount of bound radioactivity in microsome increased significantly.
The results in vitro studies suggested that the amount of bound radioactivity varies with the reaction time and the concentration of microsomal protein in the incubation mixture. The amount of bound radioactivity decreased when NADPH was absent or microsomes were preheated (at 90°Ctot 10 min) or high concentration of unlabelled malathion was added to the incubation mixture.
From the above it can be seen that the binding of malathion to tissue macromolecules is mediated by a cytochrome P-450 linked MFO system. It is likely that the MFO converts malathion into chemically activated material(s) which subsequently binds to tissue macromolecules.
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