Glutathione as a protective factor in the cadmium response of human lung carcinoma cells
Human lung carcinoma derived A549 cells were studied to determine if their high cadmium resistance relative to most cells is due to their concomitantly higher level of glutathione (GSH). Cellular GSH was 75-85% and 70-80% depleted by exposing A549-T27 cells to 0.5 mM diethylmaleate (DEM) for 4 hours and 10 mM buthionine sulfoximine (BSO) for 8 hours, respectively. Such GSH depletion sensitized the cells to cadmium. The threshold of 5 ..mu..M cadmium for cytotoxic response was eliminated and the LD/sub 50/ was decreased from 31 ..mu..M to 15 and 21 ..mu..M, respectively, in DEM and BSO treated cells. There is no difference in GSH content between a cadmium resistant subpopulation (T27) of A549 and one which is more sensitive (T20). These subpopulations have the same cadmium uptake and kinetics of metallothionein synthesis. However, GSH kinetics following exposure to 5 ..mu..M cadmium differs significantly between the two subpopulations. The results suggest that a higher level of GSH may be an important, but not exclusive, determinant of greater cadmium resistance in A549 cells and that the difference in GSH metabolism may be a determinant of clonal variation of cadmium cytotoxic response in the A549 cells.
- Research Organization:
- Iowa State Univ., Ames
- OSTI ID:
- 6015491
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 46:6; ISSN FEPRA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
BIOLOGICAL EFFECTS
CADMIUM
DRUGS
ELEMENTS
GLUTATHIONE
METABOLISM
METALS
ORGANIC COMPOUNDS
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOPROTECTIVE SUBSTANCES
SENSITIVITY
TOXICITY
TUMOR CELLS