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

British Journal of Cancer

Volumn 73, Issue 4, 1996, Pages 499-505

  Hejmadi, M V ^a   McKeown, S R ^a   Friery, O P ^a   McIntyre, I A ^a   Patterson, L H ^b   Hirst, D G ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b DE MONTFORT UNIVERSITY   (United Kingdom)

Author keywords

AQ4N; Bioreductive drug; DNA damage

Indexed keywords

1,4 BIS[[2 (DIMETHYLAMINO N OXIDE)ETHYL]AMINO] 5,8 DIHYDROXYANTHRAQUINONE; ANTHRAQUINONE; DNA TOPOISOMERASE (ATP HYDROLYSING); UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL; CELL CYCLE; CELL DAMAGE; CELL HYPOXIA; CONTROLLED STUDY; CYTOTOXICITY; DNA DAMAGE; DRUG ACTIVITY; ENZYME INHIBITION; FEMALE; INTRAPERITONEAL DRUG ADMINISTRATION; KINETICS; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION; RADIATION INJURY; REDUCTION;

EID: 0030022191     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: 10.1038/bjc.1996.87     Document Type: Article

References (17)

1. BUSH RS, JENKIN RDT, ALLT WEC, BEALE FA, BEAN H, DENBO AJ AND PRINGLE JF. (1978). Definite evidence for hypoxic cells influencing cure in cancer therapy. Br. J. Cancer, 37 (suppl III), 302-306.
2. COLLARD J, MATHEW AM, DOUBLE JA AND BIBBY MV. (1995). E09: Relationship between DT-diaphorase levels and response in vitro and in vivo. Br. J. Cancer, 71, 1199-1203.
3. DESNOYES R, GILES Y, SYKES HR, PATTERSON LH AND SMITH PJ. (1993). Evaluation of a series of novel mitoxantrone analogues with modified DNA binding properties: DNA synthesis inhibition and DNA topoisomerase II poisoning. Br. J. Cancer (suppl XX), 75.
4. KRUPSKI G, KIEFER F AND WEIBEL FJ. (1985). Variability in the expression of xenobiotic metabolising enzymes during the growth cycle of rat hepatoma cells. Xenobiotica, 15, 781-787.
5. MCALEER JJA, MCKEOWN SR, MACMANUS MP, LAPPIN TRJ AND BRIDGES JM. (1992). Hypobaric hypoxia: a method for testing bioreductive drugs in vivo. Int. J. Radiat. Oncol. Biol. Phys., 23, 551-555.
6. MCKELVEY-MARTIN VJ, GREEN MHL, SCHMEZER P, POOL-ZOBEL BL, DE MEO MP AND COLLINS A. (1993). The single cell gel electrophoresis assay (comet assay): A European review. Mutat. Res., 288, 47-63.
7. MCKEOWN SR, HEJMADI MV, MCINTYRE IA, MCALEER JJA AND PATTERSON LH. (1995). AQ4N: an alkylaminoanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo. Br. J. Cancer, 72, 76-81.
8. MOORE JV. (1988). The dynamics of tumour cords in an irradiated mouse mammary carcinoma with a large hypoxic cell component. Jpn. J. Cancer Res. (Gann) 79, 236-243.
9. OKUNIEFF P, HOECKEL M, DUNPHY EP, SCHLENGER K, KNOOP C AND VAUPEL P. (1993). Oxygen tension distributions are sufficient to explain the local response of human breast tumors treated with radiation alone. Int. J. Radiat. Oncol. Biol. Phys., 26, 631-636.
10. OLIVE PL, BANATH JP AND DURAND RE. (1990). Heterogeneity in radiation induced DNA damage and repair in tumour and normal cells measured using the Comet assay. Radiat. Res., 122, 86-94.
11. OLIVE PL AND BANATH JP. (1992). Growth fraction measured using the Comet Assay. Cell Prolif., 25, 447-457.
12. OLIVE PL. (1994). Radiation-induced reoxygenation in the SCVII murine tumour: evidence for a decrease in oxygen consumption and an increase in tumour perfusion. Radiother. Oncol, 32, 37-46.
13. PATTERSON LH. (1993). Rationale for the use of aliphatic N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastis Rev., 12, 119-134.
14. PATTERSON LH, CRAVEN MR, FISHER GR AND TEESDALE-SPITTLE P. (1994). Aliphatic amine N-oxides of DNA binding agents as bioreductive drugs. Oncol. Res., 6, 533-538.
15. SINGH NP, MCCOY MT, TICE RR AND SCHNEIDER EL. (1988). A simple method for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res., 175, 184-191.
16. WHITAKER SJ, POWELL SN AND MCMILLAN TJ. (1991). Molecular assays of radiation-induced DNA damage. Eur. J. Cancer, 27, 922-928.
17. WORKMAN P AND STRATFORD IJ. (1993). The experimental development of bioreductive drugs and their role in cancer therapy. Cancer Metastis Rev., 12, 73-82.