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- Title
Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine.
- Authors
Friery, O P; Gallagher, R; Murray, M M; Hughes, C M; Galligan, E S; McIntyre, I A; Patterson, L H; Hirst, D G; McKeown, S R
- 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[SUP-1]) in combination with cyclophosphamide (100 mg kg[SUP-1]) produced an effect equivalent to a single 200 mg kg[SUP-1])dose of cyclophosphamide. Tirapazamine (25 mg kg[SUP-1]) in combination with cyclophosphamide (100 mg kg[SUP-1]) produced an effect equivalent to a single 150 mg kg[SUP-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[SUP-1]); AQ4N (50-200 mg kg[SUP-1]) produced a more effective combination than tirapazamine (12.5-50 mg kg[SUP-1]). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg[SUP-1]) 6 h prior to cyclophosphamide (100 mg kg[SUP-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[SUP-1]).
- Subjects
DRUG efficacy; MOUSE diseases; TUMORS
- Publication
British Journal of Cancer, 2000, Vol 82, Issue 8, p1469
- ISSN
0007-0920
- Publication type
Article
- DOI
10.1054/bjoc.1999.1132