Changes in energy metabolism and X-ray sensitivity in murine tumours by the nitric oxide donor SIN-1.
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.
Wood
P J
PJ
MRC Radiobiology Unit, Chilton, Didcot, Oxon, UK.
Sansom
J M
JM
Stratford
I J
IJ
Adams
G E
GE
Szabo
C
C
Thiemermann
C
C
Vane
J R
JR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000532:radiotherapy*; D009569:Nitric Oxide / Q000502:physiology*; D011836:Radiation Tolerance / Q000187:drug effects*
D009569:Nitric Oxide; C002385:linsidomine; D008981:Molsidomine