Studies on the mechanism of cytotoxicity of 3-deazaguanosine in human cancer cells

The mechanism of toxicity of 3-deazaguanosine was studied in a number of human tumor cell lines by determination of the effects of various purine compounds on the growth of the cells in the presence of the drug and by studies of the effects of 3-deazaguanosine on the metabolism of radiolabeled precu...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 1985-05, Vol.15 (1), p.59-62
Main Authors: PAGE, T, JACOBSEN, S. J, SMEJKAL, R. M, SCHEELE, J, NYHAN, W. L, MANGUM, J. H, ROBINS, R. K
Format: Article
Language:English
Subjects:
Adenine - metabolism
Antineoplastic agents
Biological and medical sciences
Cell Division - drug effects
Cells, Cultured
DNA - biosynthesis
Formates - metabolism
General aspects
GMP Reductase
Guanine - metabolism
Guanosine - analogs & derivatives
Guanosine - pharmacology
Humans
Medical sciences
NADH, NADPH Oxidoreductases - metabolism
Neoplasms - drug therapy
Pharmacology. Drug treatments
Purines - pharmacology
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Summary:The mechanism of toxicity of 3-deazaguanosine was studied in a number of human tumor cell lines by determination of the effects of various purine compounds on the growth of the cells in the presence of the drug and by studies of the effects of 3-deazaguanosine on the metabolism of radiolabeled precursors in these cells. The drug was found to be toxic to all of the cell lines tested. The toxicity was reversible with removal of the drug. None of the purine bases tested could restore normal growth after 48 h exposure to 3-deazaguanosine; the bases were more effective in preventing cytotoxicity when added simultaneously with the drug. Metabolic studies indicated decreased synthesis of DNA, variable inhibition of de novo purine synthesis, and complete inhibition of the enzyme guanosine monophosphate reductase by 3-deazaguanosine.
ISSN:0344-5704
1432-0843
DOI:10.1007/BF00257296