Mechanism of detoxication of some organophosphorus compounds: the role of glutathione-dependent demethylation

Abstract

The detoxication of the geometrical isomers of Bomyl® (dimethyl-1,3-dicarbomethoxy-1-propen-2-yl phosphate) and Phosdrin® (mevinphos, dimethyl-1-carbomethoxy-1-propen-2-yl phosphate) by mouse liver has been studied. Most of the degrading activity for Phosdrin isomers was found in the supernatant fraction, whereas for Bomyl isomers it was equally distributed between the microsomal and the supernatant fractions. cis-Phosdrin is degraded in a system which requires reduced glutathione, the metabolites being cis-monomethyl-1-carbomethoxy-1-propen-2-yl phosphate (cis-desmethyl-Phosdrin)and S-methylglutathione. On the other hand, tras-Phosdrin and both Bomyl isomers were degraded to dimethyl phosphate. A method for the synthesis of cis-thiono-Bomyl is also reported. The possible general role of glutathione in the degradation of organophosphorus compounds is discussed.