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DNA damage following combination of radiation with the bioreductive drug AQ4N: Possible selective toxicity to oxic and hypoxic tumour cells

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Hejmadi, MV, McKeown, SR, Friery, OP, McIntyre, Irene, Patterson, LH and Hirst, DG (1996) DNA damage following combination of radiation with the bioreductive drug AQ4N: Possible selective toxicity to oxic and hypoxic tumour cells. British Journal of Cancer , 73 (4). pp. 499-505. [Journal article]

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Abstract

AQ4N (1,4-bis-{[2-(dimethylamino-N-oxide)ethyl]amino}5,8-dihydroxyanthrac ene-9,10-dione) is a novel bioreductive agent that can be reduced to a stable, DNA-affinic compound, AQ4. The alkaline comet assay was used to evaluate DNA damage induced by AQ4N and radiation. Cells prepared from freshly excised T50/80 murine tumours were shown to have the ability to reduce AQ4N to a DNA-damaging agent; this had disappeared within 24 h of excision. When T50/80 tumours implanted in BDF mice were exposed to radiation in vivo a considerable amount of DNA damage was present in tumours excised immediately. Minimal levels of DNA damage were detectable in tumours excised after 2-5 h. AQ4N given 30 min before radiation had no appreciable influence on this effect and AQ4N alone caused only a small amount of damage. When AQ4N and radiation were combined an increasing number of damaged cells were seen in tumours excised 24-96 h after irradiation. This was interpreted as evidence of the continued presence of AQ4, or AQ4-induced damage, which was formed in cells hypoxic at the time of administration of AQ4N. AQ4, a potent topoisomerase II inhibitor, would be capable of damaging cells recruited into the cell cycle following radiation damage to the well-oxygenated cells of the tumour. The kinetics of the expression of the DNA damage is consistent with this hypothesis and shows that AQ4 has persistent activity in vivo.

Item Type:Journal article
Keywords:DNA damage; bioreductive drug; AQ4N
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Health Sciences
Research Institutes and Groups:Institute of Nursing and Health Research > Centre for Health and Rehabilitation Technologies
ID Code:15093
Deposited By:Miss Anna Mooney
Deposited On:31 Aug 2010 13:01
Last Modified:01 Mar 2012 09:42

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