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Biochemical pharmacology and experimental chemotherapy studies with guanine-7-oxide, a novel purine antibiotic.

Abstract
1. Guanine-7-oxide is a novel purine antibiotic produced by a Streptomyces species, ATCC 39364. 2. Guanine-7-oxide is cytotoxic to murine and human leukemia cells in vitro at sub-micromolar concentrations. Murine and human carcinoma cells are much less sensitive. 3. Guanine-7-oxide has significant in vivo antitumor activity, particularly against the intraperitoneal and subcutaneous L1210 leukemia systems. 4. Guanine-7-oxide, at highly cytotoxic concentrations, has little effect on biosynthesis of RNA and DNA. 5. There is preliminary evidence for an early effect of guanine-7-oxide on cellular protein synthesis. 6. Guanine, guanosine and hypoxanthine protect cells from the cytotoxicity of guanine-7-oxide. 7. Activation of guanine-7-oxide requires the presence of the enzyme hypoxanthine-guanine phosphoribosyltransferase in the target cells. 8. Cytotoxic concentrations of guanine-7-oxide do not cause depletion of cellular guanine nucleotides during a two hr incubation period. 9. Guanine-7-oxide is converted within mouse and human cells to a metabolite with chromatographic mobility corresponding to a ribonucleoside 5'-triphosphate.
AuthorsR C Jackson, T J Boritzki, J A Besserer, K L Hamelehle, J L Shillis, W R Leopold, D W Fry
JournalAdvances in enzyme regulation (Adv Enzyme Regul) Vol. 26 Pg. 301-16 ( 1987) ISSN: 0065-2571 [Print] England
PMID3673707 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Antibiotics, Antineoplastic
  • Neoplasm Proteins
  • Ribonucleotides
  • guanine 7-oxide
  • Guanine
Topics
  • Animals
  • Antibiotics, Antineoplastic (therapeutic use)
  • Cell Line
  • Cell Survival (drug effects)
  • Female
  • Guanine (analogs & derivatives, therapeutic use)
  • Humans
  • Leukemia L1210 (metabolism)
  • Leukemia, Experimental (drug therapy)
  • Mice
  • Neoplasm Proteins (biosynthesis)
  • Neoplasms, Experimental (drug therapy, pathology)
  • Ribonucleotides (analysis)

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