Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis

Yujian Kang, Jeffrey A. Clapper, M. Duane Enger

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-727) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd+-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20% to 25% of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This observation also raises the possibility that intracellular cysteine levels limit Cd++-induced MT accumulation rates.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalCell Biology and Toxicology
Volume5
Issue number3
DOIs
StatePublished - Nov 1 1989

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Metallothionein
Cytotoxicity
Cadmium
Glutathione
Buthionine Sulfoximine
diethyl maleate
Cysteine
Cytoprotection
Level control
A549 Cells
Carcinoma
Lung

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Cell Biology
  • Health, Toxicology and Mutagenesis

Cite this

Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis. / Kang, Yujian; Clapper, Jeffrey A.; Enger, M. Duane.

In: Cell Biology and Toxicology, Vol. 5, No. 3, 01.11.1989, p. 249-259.

Research output: Contribution to journalArticle

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abstract = "Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-727) cells to the cytotoxic effects of Cd++. The effects of GSH depletion on Cd++ accumulation and Cd+-induced metallothionein (MT) content were investigated to determine the possible role of these Cd++ responses in the sensitization process. Cellular GSH was depleted to 20{\%} to 25{\%} of control levels with buthionine sulfoximine (BSO), or diethyl maleate (DEM), respectively. Neither treatment significantly affected Cd++-induced accumulation of exogenous35s-cysteine into intracellular MT in a dose-dependent fashion. The results indicate that neither enhanced Cd++ accumulation nor reduced MT synthesis plays a primary role in affecting enhanced Cd++ cytotoxicity in A549 cells with reduced GSH levels. Although BSO inhibition of GSH synthesis enhanced MT synthesis, it sensitized the cells to Cd++, which suggests an additive effect of GSH and MT in cadmium cytoprotection. This observation also raises the possibility that intracellular cysteine levels limit Cd++-induced MT accumulation rates.",
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