Glutathione is involved in the early cadmium cytotoxic response in human lung carcinoma cells.
Depletion of cellular glutathione (GSH) has been shown to sensitize A549-T27 human tumor cells to the cytotoxic effects of Cd2+. In this study the temporal and quantitative relationships between reduced cellular GSH levels and cadmium cytotoxic response in these cells were further investigated. Exposure of A549-T27 cells to 10 mM buthionine sulfoximine (BSO) for 8 h decreased their GSH level by 65%. This GSH level remained relatively constant for 8 h in the presence or absence of BSO, but recovered to 83% of the normal cellular level 24 h after removal of BSO. Exposure to 5 microM Cd2+ for 8 h did not significantly change cellular GSH levels. Pretreatment of the A549-T27 cells with 10 mM BSO for 8 h and subsequent exposure of the cells to Cd2+ for 10 days, with or without concurrent treatment of 10 mM BSO during the first 8 h of Cd2+ exposure, resulted in disappearance of the 5 microM Cd2+ threshold for cytotoxic response and reduction of the LC50 from 31 microM Cd2+ to 21 microM. Similar results were obtained when BSO pretreated cells were exposed to Cd2+ for 8 h. The threshold for cytotoxic response of 10 microM Cd2+ disappeared and the LC50 was reduced from 60 microM to 29 microM Cd2+ (with concurrent BSO treatment) and 30 microM (BSO pretreatment only). The results show that GSH plays an important role in early cellular protective responses to Cd2+.
Kang
Y J
YJ
Department of Zoology, Iowa State University, Ames 50011.
Enger
M D
MD
D019328:Buthionine Sulfoximine; D002104:Cadmium / Q000633:toxicity*; D004347:Drug Interactions; D005978:Glutathione / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000633:toxicity
D002104:Cadmium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione