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Synergistic enhancement of 6-thioguanine cytotoxicity by ADP-ribosyltransferase inhibitors

Lookup NU author(s): Professor barbara Durkacz

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Abstract

The effect of the adenosine diphosphoribosyltransferase inhibitors, the substituted benzamides, on the cytotoxicity of 6-thioguanine (6TG) was investigated. Nontoxic concentrations of benzamides potentiated the cytotoxicity of 6TG with a dose enhancement factor of 2, producing a 6-fold increase in cell killing at 10% survival. 6TG treatment did not deplete cellular NAD levels, and in the presence of 3-aminobenzamide, there was no increase in the number of 6TG-induced DNA strand breaks. To obtain potentiation of cytotoxicity, 3-aminobenzamide had to be present in late G1-S phase during the cell cycle in which 6TG is incorporated into the DNA. These data indicate that the substituted benzamides potentiate the cytotoxicity of 6TG by a mechanism independent of an inhibition of DNA repair.

Publication metadata

Author(s): Moses K, Harris AL, Durkacz BW

Publication type: Article

Publication status: Published

Journal: Cancer Research

Year: 1988

Volume: 48

Issue: 20

Pages: 5650-5654

Print publication date: 01/10/1988

ISSN (print): 0008-5472

ISSN (electronic): 1538-7445

URL: http://cancerres.aacrjournals.org/cgi/content/abstract/48/20/5650

PubMed id: 3139280

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