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

Journal Article · · Cell Biology and Toxicology; (USA)
DOI:https://doi.org/10.1007/BF01795354· OSTI ID:7244178
; ;  [1]
  1. Iowa State Univ., Ames (USA)
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Glutathione (GSH) depletion sensitizes human lung carcinoma (A549-T27) 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 exogenous 35s-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.

OSTI ID:
7244178
Journal Information:
Cell Biology and Toxicology; (USA), Journal Name: Cell Biology and Toxicology; (USA) Vol. 5:3; ISSN CBTOE; ISSN 0742-2091
Country of Publication:
United States
Language:
English

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Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL ACCUMULATION
BIOLOGICAL EFFECTS
BODY
CADMIUM
CARBOXYLIC ACIDS
CYSTEINE
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
GLUTATHIONE
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LUNGS
MAMMALS
MAN
METALLOPROTEINS
METALLOTHIONEIN
METALS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PEPTIDES
POLYPEPTIDES
PRIMATES
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RESPIRATORY SYSTEM
SULFUR 35
SULFUR ISOTOPES
THIOLS
TOXICITY
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES