Guanine ribonucleotide depletion in mammalian cells. A target of purine antimetabolites.

In a previous report we demonstrated in mouse lymphoma (S-49) cells that DNA synthesis inhibition resulting from guanine starvation is associated with GTP rather than dGTP depletion. Since several effective anticancer drugs act via guanine depletion, it is important to test whether critical GTP depletion is unique to S-49 cells or also occurs in other cell lines. Mycophenolic acid-induced guanine starvation caused a drastic DNA synthesis inhibition in the human lymphoblastic T leukemia (CEM) and the mouse B leukemia (L1210) cell lines, which was again associated with GTP depletion rather than dGTP depletion. These results suggest that GTP depletion represents a common target of purine antimetabolites in mammalian cells.
AuthorsB T Nguyen, M B Cohen, W Sadée
JournalCancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 11 Issue 2 Pg. 117-9 ( 1983) ISSN: 0344-5704 [Print] GERMANY, WEST
PMID6578881 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • DNA, Neoplasm
  • Guanosine
  • Guanosine Triphosphate
  • Deoxyguanosine
  • Mycophenolic Acid
  • Animals
  • Cell Division (drug effects)
  • DNA, Neoplasm (biosynthesis)
  • Deoxyguanosine (pharmacology)
  • Guanosine (pharmacology)
  • Guanosine Triphosphate (metabolism)
  • Humans
  • Leukemia L1210 (metabolism)
  • Leukemia, Lymphoid (metabolism)
  • Mice
  • Mycophenolic Acid (pharmacology)

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