Pesticides as activators of mouse liver microsomal glutathione S-transferase

Abstract

Selected sulfhydryl-reactive pesticides activate mouse liver microsomal glutathione S-transferase (GST m) assayed in purified form free from cytosolic transferases (GST cs) with 1-chloro-2,4-dinitrobenzene as the substrate. Maximum activations were as follows: 1315% for N-ethylmaleimide (positive control) at 1 m M, 374% for chloranil at 0.01 m M, 272% for EPTC sulfoxide at 10 m M, 255% for captan at 0.1 m M, 228% for acrolein at 1 m M, and 152% for methyl isothiocyanate at 10 m M. Pesticides which showed little or no activation were alachlor, atrazine, tetramethrin, and tridiphane. The toxicological relevance of GST m activation was examined with the aforementioned activators plus EPTC and allyl alcohol. Experiments were conducted in vitro or in vivo with washed microsomes (which contain not only GST m but also some GST cs) and the post-mitochondrial supernatant fraction with its high GST c activity. These studies established that GST m, either unactivated or activated, was not a significant contributor to overall mouse liver GST activity.