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, Csaba Szabo, C. Thiemermann, J. R. Vane

Research output: Contribution to journalArticle

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-1 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)
JournalThe British journal of cancer. Supplement
Volume27
StatePublished - Jul 1996
Externally publishedYes

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Nitric Oxide Donors
Energy Metabolism
X-Rays
Neoplasms
Injections

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Wood, P. J., Sansom, J. M., Stratford, I. J., Adams, G. E., Szabo, C., Thiemermann, C., & Vane, J. R. (1996). Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1. The British journal of cancer. Supplement, 27.

Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1. / Wood, P. J.; Sansom, J. M.; Stratford, I. J.; Adams, G. E.; Szabo, Csaba; Thiemermann, C.; Vane, J. R.

In: The British journal of cancer. Supplement, Vol. 27, 07.1996.

Research output: Contribution to journalArticle

Wood, P. J. ; Sansom, J. M. ; Stratford, I. J. ; Adams, G. E. ; Szabo, Csaba ; Thiemermann, C. ; Vane, J. R. / Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1. In: The British journal of cancer. Supplement. 1996 ; Vol. 27.
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