title: The effects of sodium diethyldithiocarbamate in fibroblasts V79 cells in relation to cytotoxicity, antioxidative enzymes, glutathione, and apoptosis.
abstract: Sodium diethyldithiocarbamate (DETC) is the main metabolite of disulfiram. Recently, we reported that mechanism of disulfiram cytotoxicity in V79 cells might be partially connected with thiol redox-state imbalance. Here, we examined the effect of DETC on the level of intracellular glutathione (GSH), protein oxidation (measured as PC-protein carbonyl content), lipid peroxidation (measured as TBARS-thiobarbituric acid reactive substances), antioxidant enzymatic defense, as well as on apoptosis. We used V79 Chinese hamster fibroblasts cells with and without modulated glutathione (GSH) level by N-acetyl-L-cysteine (NAC). We showed that treatment with DETC at concentrations that cause a moderate increase in thiol-state imbalance but not cell death stimulates oxidative stress measured as increased level of PC and TBARS, adaptive response of GSH-related enzymes and apoptosis. Our results show that cellular effects of DETC are partially attributable to the initial redox cellular state, since the increase of GSH level by NAC pre-treatment prevented the observed changes.
authors.affiliation: Department of Biochemistry, Medical University of Warsaw, Banacha 1, 02-097, Warsaw, Poland. iwonna.rahden-staron@wum.edu.pl
authors.forename: I
authors.initials: I
authors.lastname: Rahden-Staroń
authors.forename: E
authors.initials: E
authors.lastname: Grosicka-Maciąg
authors.forename: D
authors.initials: D
authors.lastname: Kurpios-Piec
authors.forename: H
authors.initials: H
authors.lastname: Czeczot
authors.forename: T
authors.initials: T
authors.lastname: Grzela
authors.forename: M
authors.initials: M
authors.lastname: Szumiło
mesh_terms: D000818:Animals; D017304:Annexin A5; D000975:Antioxidants / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D003124:Colorimetry; D004396:Coloring Agents; D006224:Cricetinae; D053938:DNA Fragmentation / Q000187:drug effects; D004221:Disulfiram / Q000633:toxicity; D004050:Ditiocarb / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D015227:Lipid Peroxidation / Q000187:drug effects; D050050:Protein Carbonylation; D017392:Thiobarbituric Acid Reactive Substances; D014343:Trypan Blue
chemical_list: D017304:Annexin A5; D000975:Antioxidants; D004396:Coloring Agents; D017392:Thiobarbituric Acid Reactive Substances; D004050:Ditiocarb; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D014343:Trypan Blue; D004221:Disulfiram