Comet assay studies on the activation of two diaziridinylbenzoquinones in K562 cells

Biochemical Pharmacology
T H WardJ T Richards

Abstract

Two versions of the comet assay have been used to identify the difference in the modes of action of AZQ (2,5-diaziridinyl-3,6-bis(carboethoxyamino)-1,4-benzoquinone) and BZQ (2,5-diaziridinyl-3,6-bis(ethanolamino)-1,4-benzoquinone) in human leukaemia K562 cells and a K562-derived resistant cell line, BZQR. Using the standard alkaline assay, AZQ produced dose-dependent changes in the mean comet moments from K562 cells, consistent with the formation of strand breaks. This damage was repaired over a period of 6 hr after removal of the drug. The resistant cell line, BZQR, showed much smaller changes in comet moment under identical conditions. In contrast to AZQ, BZQ did not produce any measurable strand breaks in the K562 or BZQR cells. However, the comet radiation/crosslinking assay and a fluorescence-based assay revealed that BZQ extensively cross-links DNA in K562 cells. The extent of cross-linking is greatly reduced in the resistant cell line.

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Citations

Dec 9, 2004·Biochimica Et Biophysica Acta·Jeff CummingsCaroline Dive
Oct 9, 2008·Acta Biologica Hungarica·Gabrielle de Souza RochaR Santos
Jul 28, 2004·Environmental and Molecular Mutagenesis·P Suresh KannaMalay Chatterjee
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Apr 9, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Timothy H WardJohn Butler
Mar 6, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·E RojasM Valverde

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