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–1dose 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–1dose 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 kg–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). © 2000 Cancer Research Campaign
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Friery, O., Gallagher, R., Murray, M. et al. Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. Br J Cancer 82, 1469–1473 (2000). https://doi.org/10.1054/bjoc.1999.1132
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DOI: https://doi.org/10.1054/bjoc.1999.1132
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