PMID: 8595165Feb 1, 1996Paper

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

British Journal of Cancer
M V HejmadiDavid G Hirst

Abstract

AQ4N (1,4-bis-([2-(dimethylamino-N- oxide)ethyl]amino)5,8-dihydroxyanthracene-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 wel...Continue Reading

Citations

Dec 19, 2002·Cancer Gene Therapy·Helen O McCarthyTracy Robson
Jul 1, 1997·Environmental Health and Preventive Medicine·Y LuK Morimoto
Mar 6, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·E RojasM Valverde
Jun 5, 2007·Bioorganic & Medicinal Chemistry·Robert D Bruno, Vincent C O Njar
Aug 17, 2021·Frontiers in Oncology·Yue LiXiao-Feng Li

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