Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine.
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| Abstract |
The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50-150 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 200 mg kg 1 dose of cyclophosphamide. Tirapazamine (25 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 150 mg kg(-1) dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50-200 mg kg(-1)); AQ4N (50-200 mg kg(-1)) produced a more effective combination than tirapazamine (12.5-50 mg kg(-1)). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg(-1)) 6 h prior to cyclophosphamide (100 mg k(-1)) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg(-1)).
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| Authors | O P Friery, R Gallagher, M M Murray, C M Hughes, E S Galligan, I A McIntyre, L H Patterson, D G Hirst, S R McKeown |
| Journal | British journal of cancer (Br J Cancer) Vol. 82 Issue 8 Pg. 1469-73 (Apr 2000) ISSN: 0007-0920 [Print] England |
| PMID | 10780528 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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