Studies on the Mechanism of Cytotoxicity of 3-deazaguanosine in Human Cancer Cells

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 1985 Jan 1

PMID 4006050

Citations 2

Authors

T Page

S J Jacobsen

R M Smejkal

J Scheele

W L Nyhan

J H MANGUM

R K ROBINS

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Synthesis of 2'-O-methyl-RNAs incorporating a 3-deazaguanine, and UV melting and computational studies on its hybridization properties.

Seio K, Sasami T, Tawarada R, Sekine M Nucleic Acids Res. 2006; 34(16):4324-34.

PMID: 16936323 PMC: 1636341. DOI: 10.1093/nar/gkl088.

Cloning and functional characterization of GMPR2, a novel human guanosine monophosphate reductase, which promotes the monocytic differentiation of HL-60 leukemia cells.

Zhang J, Zhang W, Zou D, Chen G, Wan T, Zhang M J Cancer Res Clin Oncol. 2003; 129(2):76-83.

PMID: 12669231 DOI: 10.1007/s00432-002-0413-7.

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