Cell Biology and Toxicology

, Volume 3, Issue 4, pp 347–360

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

  • Yu -Jian Kang
  • M. Duane Eenger
Article

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.

Key words

A549 cells buthionine sulfoximine Cd++ cytotoxicity diethyl maleate glutathione human tumor cells 

Abbreviations

BSO

DL-buthionine-(R,S)-sulfoximine

DEM

diethyl maleate

DMSO

dimethyl sulfoxide

GSH

reduced glutathione

MT

metallothionein

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Copyright information

© Princeton Scientific Publishing Co., Inc 1987

Authors and Affiliations

  • Yu -Jian Kang
    • 1
  • M. Duane Eenger
    • 1
  1. 1.Department of ZoologyIowa State UniversityAmesUSA
  2. 2.Department of ZoologyIowa State UniversityAmesUSA

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