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 compound 1,2-dichloroethane (DCE) have been proposed. One is a mixed function 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 was to investigate the role of the latter pathway for the in vivo mutagenicity of DCE in the somatic wing spot test in Drosophila melanogaster. 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 buthionine sulfoximine (BSO), an efficient inhibitor of GSH synthesis. This pretreatment decreased the GSH level to approximately 6% as compared to the control. The pretreatment also resulted in a significant decrease of the mutagenicity of DCE. Treatment of the larvae with phenobarbiturate (PB) resulted in approximately 200% induction of cytosolic GST, and a corresponding increase in the DCE mutagenicity. These results indicate that the important pathway in vivo for the mutagenicity of DCE is dependent on GSH and GST. A similar experimental protocol was used to study interactions between aflatoxin B1 (AFB) and GSH and GST. No effect of the treatment with BSO on the mutagenicity of AFB was observed, while pretreatment with PB caused a decrease of the mutagenicity of AFB.
Romert
L
L
Department of Genetics and Cellular Toxicology, Wallenberg Laboratory, University of Stockholm, Sweden.
Magnusson
J
J
Ramel
C
C
D000348:Aflatoxins / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D019328:Buthionine Sulfoximine; D004331:Drosophila melanogaster; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000502:physiology*; D005982:Glutathione Transferase / Q000502:physiology*; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009154:Mutation; D010634:Phenobarbital / Q000633:toxicity
D000348:Aflatoxins; D005025:Ethylene Dichlorides; D006843:Hydrocarbons, Chlorinated; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; C024565:ethylene dichloride; C029753:aflatoxin B2; D005982:Glutathione Transferase; D005978:Glutathione; D010634:Phenobarbital