Effect of decreased glutathione levels in hereditary glutathione synthetase deficiency on dibromoethane-induced genotoxicity in human fibroblasts.
The genotoxic effect of dibromoethane is thought to be due to glutathione S-transferase mediated metabolism. The purpose of this study was to determine whether variations in endogenous glutathione in human cells could modify the genotoxicity of dibromoethane. Genotoxicity of dibromoethane, assessed by sister chromatid exchange, was examined in normal human skin fibroblasts and fibroblasts obtained from individuals with hereditary generalized glutathione synthetase deficiency. Cell proliferation was examined as a measure of dibromoethane toxicity. The number of sister chromatid exchanges induced by dibromoethane was significantly lower in the fibroblasts with glutathione synthetase deficiency compared to control cells. Inhibition of cell proliferation was similar in the glutathione-deficient and normal fibroblasts. In conclusion, low endogenous glutathione levels are protective against dibromoethane-induced genotoxicity in human fibroblasts.
DeLeve
L D
LD
Department of Pharmacology, University of Toronto, Ontario, Canada. deleve@hsc.usc.edu
D000704:Analysis of Variance; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D015946:Ethylene Dibromide / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism*; D005981:Glutathione Synthase / Q000172:deficiency*; D006801:Humans; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000378:metabolism; D008769:Methylnitronitrosoguanidine / Q000633:toxicity*; D009153:Mutagens; D012854:Sister Chromatid Exchange; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D015946:Ethylene Dibromide; D005981:Glutathione Synthase; D005978:Glutathione