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Role of nicotinamide adenine dinucleotide and adenosine triphosphate in glucocorticoid-induced cytotoxicity in susceptible lymphoid cells.
- Source :
-
The Journal of clinical investigation [J Clin Invest] 1987 Jun; Vol. 79 (6), pp. 1558-63. - Publication Year :
- 1987
-
Abstract
- The possibility that corticosteroid cytotoxicity could be mediated by activation of poly(ADP-ribose) polymerase and consequent depletion of NAD and ATP was evaluated in steroid-sensitive S49.1 and steroid-resistant S49.143R mouse lymphoma cells and in lymphocytes from a patient with chronic lymphocytic leukemia. All cell types were shown to have the enzyme poly(ADP-ribose) polymerase and to increase activity in response to DNA strand breaks. Incubation of susceptible cells with 1 microM dexamethasone resulted in DNA strand breaks. Susceptible cells also showed a dose-dependent decrease in NAD and ATP that preceded loss of cell viability. These studies suggest that steroid-induced cytotoxicity in susceptible lymphocytes is due to the presence of DNA strand breaks that activate poly(ADP-ribose) polymerase to a sufficient degree to consume cellular pools of NAD with a consequent depletion of ATP and loss of cell viability.
- Subjects :
- Animals
Cell Line
Cell Survival drug effects
DNA Repair
DNA, Neoplasm drug effects
Enzyme Activation
Humans
Leukemia, Lymphoid
Lymphocytes metabolism
Lymphoma
Mice
Poly(ADP-ribose) Polymerases metabolism
Adenosine Triphosphate physiology
DNA Damage
Dexamethasone pharmacology
Lymphocytes drug effects
NAD physiology
Nucleoside Diphosphate Sugars metabolism
Poly Adenosine Diphosphate Ribose metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9738
- Volume :
- 79
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of clinical investigation
- Publication Type :
- Academic Journal
- Accession number :
- 3108318
- Full Text :
- https://doi.org/10.1172/JCI112989