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

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,...

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Bibliographic Details
Published in:Biochemical pharmacology 1997-04, Vol.53 (8), p.1115-1121
Main Authors: Ward, Timothy H., Butter, John, Shahbakhti, Hassan, Richards, John T.
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic agents
Antineoplastic Agents - pharmacology
Aziridines - pharmacology
aziridinylquinones
AZQ
Benzoquinones - pharmacology
Biological and medical sciences
BZQ
Chemotherapy
comet
Cross-Linking Reagents - pharmacology
DNA Damage
DNA Repair
Drug Resistance
Electrophoresis, Agar Gel - methods
General pharmacology
Humans
Medical sciences
Pharmacology. Drug treatments
quinones
resistance
SCGE
Tumor Cells, Cultured
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Summary: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.
ISSN:0006-2952
1873-2968
DOI:10.1016/S0006-2952(96)00818-0