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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Abbreviations
- GSH:
-
glutathione
- MT:
-
metallothionein
- BSO:
-
DL-buthionine-[S,R]-sulfoximine
- DMSO:
-
dimethyl sulfoximine
- DEM:
-
diethyl maleate
- NP-40:
-
nonidet-P40
- PBS:
-
phosphate buffered saline
- HBSS:
-
Hank's balanced salt solution
- DTT:
-
dithiothreitol
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3. This work was presented in part at the 72nd Annual Meeting of the Federation of American Societies for Experimental Biology, Las Vegas, Nevada, May 1–5, 1988.
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Kang, YJ., Clapper, J.A. & Enger, M.D. Enhanced cadmium cytotoxicity in A549 cells with reduced glutathione levels is due to neither enhanced cadmium accumulation nor reduced metallothionein synthesis. Cell Biol Toxicol 5, 249–259 (1989). https://doi.org/10.1007/BF01795354
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DOI: https://doi.org/10.1007/BF01795354