Failure of chronic glutathione elevation to reduce cytotoxicity produced by exposure to cis-diamminedichloroplatinum(II), ionizing radiation, or hyperthermia.

Freeman ML, Meredith MJ, Eisert DR
Cancer Res. 1990 50 (17): 5296-300

PMID: 1974822

Chinese hamster ovary (CHO) cells cultured in vitro were continuously exposed to increasing concentrations of diethylmaleate (DEM). Chronic exposure of these cells (designated CHO/DEM) to 80 microM diethylmaleate resulted in an increase in cystine transport, a decrease in glutathione inhibition of the enzyme gamma-glutamylcysteine synthetase, elevation of intracellular glutathione levels to 4.3 times control, and elevation of glutathione-S-transferase activity by 6.6 times. Yet, CHO/DEM and control CHO cells exhibited the same ability to synthesize protein as measured by two-dimensional electrophoresis, the same cell cycle distribution, and the same population doubling times. CHO/DEM cells are resistant to DEM and diamide cytotoxicity, compared to control CHO cells. CHO/DEM cells were used to address the question of whether chronic elevation of glutathione, above control concentrations, reduced the cytotoxicity produced by exposure to cisplatin, gamma-radiation, or hyperthermia. The resulting dose-response curves obtained with CHO/DEM and control CHO cells indicated that chronic exposure to DEM, which resulted in chronic elevation of glutathione, did not provide protection against any of the three toxic treatments.

MeSH Terms (21)

Animals Biological Transport Cell Cycle Cell Line Cell Survival Cisplatin Cricetinae Cricetulus Cystine Feedback Female Gamma Rays Glutamate-Cysteine Ligase Glutathione Glutathione Transferase Hot Temperature Kinetics Maleates Ovary Protein Biosynthesis Proteins

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