Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

OP Friery, R Gallagher, MM Murray, Ciara Hughes, ES Galligan, Irene McIntyre, LH Patterson, DG Hirst, Stephanie McKeown

Research output: Contribution to journalArticle

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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 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)). (C) 2000 Cancer Research Campaign.
LanguageEnglish
Pages1469-1473
JournalBRITISH JOURNAL OF CANCER
Volume82
Issue number8
Publication statusPublished - Apr 2000

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tirapazamine
Cyclophosphamide
Pharmaceutical Preparations
Neoplasms
Bone Marrow Cells
AQ4N
Inbred C3H Mouse

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Friery, OP., Gallagher, R., Murray, MM., Hughes, C., Galligan, ES., McIntyre, I., ... McKeown, S. (2000). Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. BRITISH JOURNAL OF CANCER, 82(8), 1469-1473.
Friery, OP ; Gallagher, R ; Murray, MM ; Hughes, Ciara ; Galligan, ES ; McIntyre, Irene ; Patterson, LH ; Hirst, DG ; McKeown, Stephanie. / Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. In: BRITISH JOURNAL OF CANCER. 2000 ; Vol. 82, No. 8. pp. 1469-1473.
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Friery, OP, Gallagher, R, Murray, MM, Hughes, C, Galligan, ES, McIntyre, I, Patterson, LH, Hirst, DG & McKeown, S 2000, 'Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine', BRITISH JOURNAL OF CANCER, vol. 82, no. 8, pp. 1469-1473.

Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. / Friery, OP; Gallagher, R; Murray, MM; Hughes, Ciara; Galligan, ES; McIntyre, Irene; Patterson, LH; Hirst, DG; McKeown, Stephanie.

In: BRITISH JOURNAL OF CANCER, Vol. 82, No. 8, 04.2000, p. 1469-1473.

Research output: Contribution to journalArticle

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T1 - Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine

AU - Friery, OP

AU - Gallagher, R

AU - Murray, MM

AU - Hughes, Ciara

AU - Galligan, ES

AU - McIntyre, Irene

AU - Patterson, LH

AU - Hirst, DG

AU - McKeown, Stephanie

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N2 - 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 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)). (C) 2000 Cancer Research Campaign.

AB - 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 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)). (C) 2000 Cancer Research Campaign.

M3 - Article

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EP - 1473

JO - BRITISH JOURNAL OF CANCER

T2 - BRITISH JOURNAL OF CANCER

JF - BRITISH JOURNAL OF CANCER

SN - 0007-0920

IS - 8

ER -

Friery OP, Gallagher R, Murray MM, Hughes C, Galligan ES, McIntyre I et al. Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. BRITISH JOURNAL OF CANCER. 2000 Apr;82(8):1469-1473.