The importance of glutathione and glutathione transferase for somatic mutations in Drosophila melanogaster induced in vivo by 1,2-dichloroethane

Two principal pathways of metabolism of the carcinogenic compoundl,2-dichloroethane (DCE) have been proposed. One is a mixedfunction oxidase dependent pathway requiring oxygen and NADPH.The other pathway depends on the presence of glutathione (GSH)and glutathione transferase (GST). The aim of this study wasto investigate the role of the latter pathway for the in vivomutagenicity of DCE in the somatic wing spot test in Drosophilamelanogaster. DCE caused a dose-dependent increase of wing spots.In order to investigate the role of cellular GSH for the mutagenicity,the level of GSH was decreased by 24 h pretreatment with buthioninesulfoximine (BSO), an efficient inhibitor of GSH synthesis.This pretreatment decreased the GSH level to 6% as comparedto the control. The pretreatment also resulted in a significantdecrease of the mutagenicity of DCE. Treat ment of the larvaewith phenobarbiturate (PB) resulted in 200% induction of cytosolicGST, and a corresponding increase in the DCE mutagenicity. Theseresults indicate that the important pathway in vivo for themutagenicity of DCE is dependent on GSH and GST. A similar experimentalprotocol was used to study interactions between aflatoxin B₁(AFB) and GSH and GST. No effect of the treatment with BSO onthe mutagenicity of AFB was observed, while pretreatment withPB caused a decrease of the mutagenicity of AFB.