Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1

P. J. Wood, J. M. Sansom, I. J. Stratford, G. E. Adams, C. Szabo, C. Thiemermann, J. R. Vane

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    13 Scopus citations

    Abstract

    The effect of the nitric oxide (NO) donor SIN-1 on energy metabolism was examined in three murine transplantable tumours in vivo using 31P MRS. SIN-1 at 2 mg kg-1 i.v. reduced Pi/total by 40-50% in SCCVII/Ha and KHT tumours within 5 min of injection, returning to control levels by 20 min. However, this dose of SIN-1 did not consistently alter Pi/total in RIF-1 tumours. Reduction in Pi/total in SCCVII/Ha tumours 10 min after 5 mg kg-l i.v. SIN-1 was similar to that for 2 mg kg-1. SIN-1 at 10 mg kg-1 had no effect on Pi/total at 10 min after injection, but increased this ratio 2-fold over control at 60 min, at which time no effect of the lower doses of SIN-1 were observed. SIN-1 effects on SCCVII/Ha tumour response to X-rays were also examined, using an in vivo/in vitro clonogenic assay 24 h after treatment. SIN-1 at 0.5-2 mg kg-1 i.v. given immediately before irradiation increased tumour cell killing 2-4-fold over that for 15 Gy X-rays alone, while higher SIN-1 doses were ineffective. The results indicate that NO donors can alter tumour energy metabolism and X-ray response in a manner consistent with increased oxygenation. However, these responses are dependent upon dose, timing and tumour type.

    Original languageEnglish (US)
    Pages (from-to)S177-S180
    JournalBritish Journal of Cancer
    Volume74
    Issue numberSUPPL. XXVII
    StatePublished - Jan 1 1996

    Keywords

    • Nitric oxide
    • Tumour oxygenation
    • Vascular tone

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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