Effect of cellular glutathione depletion on cadmium-induced cytotoxicity in human lung carcinoma cells

Yujian Kang, M. Duane Eenger

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The effect of glutathione depletion on cellular toxicity of cadmium was investigated in a subpopulation (T27) of human lung carcinoma A549 cells with coordinately high glutathione levels and Cd++-resistance. Cellular glutathione levels were depleted by exposing the cells to diethyl maleate or buthionine sulfoximine. Depletion was dose-dependent. Exposure of the cells to 0.5 mM diethyl maleate for 4 hours or to 10 mM buthionine sulfoximine for 8 hours eliminated the threshold for Cd++ cytotoxic effect and deccreased the LD50S. Cells that were pretreated with 0.5 mM diethyl maleate or 10 mM buthionine sulfoximine and then exposed to these same concentrations of diethyl maleate or buthionine sulfoximine during the subsequent assay for colony forming efficiency produced no colonies, reflecting an enhanced sensitivity to these agents at low cell density. Diethyl maleate was found to be more cytotoxic than buthionine sulfoximine. Synergistic cytotoxic effects were observed in the response of diethyl maleate pretreated cells exposed to Cd++. Thus the results demostrated that depletion of most cellular glutathione in A549-T27 cells prior to Cd++ exposure sensitizes them to the agent's cytotoxic effects. Glutathione thus may be involved in modulating the early cellular Cd++ cytotoxic response. Comparison of reduced glutathione levels and of Cd++ cytotoxic responses in buthionine sulfoximine-treated A549-T27 cells with those levels in other, untreated normal and tumor-derived cells suggests that the higher level of glutathione in A549-T27 is not the sole determinant of its higher level of Cd++ resistance.

Original languageEnglish (US)
Pages (from-to)347-360
Number of pages14
JournalCell Biology and Toxicology
Volume3
Issue number4
DOIs
StatePublished - Dec 1 1987
Externally publishedYes

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diethyl maleate
Buthionine Sulfoximine
Cytotoxicity
Cadmium
Glutathione
Cells
Carcinoma
Lung
Cytotoxins
Toxicity
Tumors
Assays
Cell Count

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

Cite this

Effect of cellular glutathione depletion on cadmium-induced cytotoxicity in human lung carcinoma cells. / Kang, Yujian; Eenger, M. Duane.

In: Cell Biology and Toxicology, Vol. 3, No. 4, 01.12.1987, p. 347-360.

Research output: Contribution to journalArticle

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