Modification of energy metabolism and radiation response of a murine tumour by changes in nitric oxide availability.
The nitric oxide donor, SIN-1 and nitric oxide synthase inhibitor, nitro-L-arginine were examined for their effects on energy metabolism using 31P magnetic resonance spectroscopy, and on radiation sensitivity in the transplantable murine tumour, SCCVII/Ha. SIN-1 at 2 mg/kg i.v. reduced Pi/total by 40-50% within 10 min and increased X-ray sensitivity 3 fold, consistent with increased tumour oxygenation. Nitro-L-arginine at 10 mg/kg i.v. increased Pi/total by 250% at 45 min and was maintained for at least 2 hr. Nitro-L-arginine also increased radiation resistance 3-5 fold, consistent with the induction of tumour hypoxia. The results indicate that tumour energy metabolism may be altered through drug induced modification of nitric oxide availability, and that these changes are sufficient to modify tumour sensitivity to X-rays.
Wood
P J
PJ
MRC Radiobiology Unit, Didcot, Oxon, United Kingdom.
Stratford
I J
IJ
Adams
G E
GE
Szabo
C
C
Thiemermann
C
C
Vane
J R
JR
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001682:Biological Availability; D015687:Cell Hypoxia; D004734:Energy Metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008809:Mice, Inbred C3H; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine; D011836:Radiation Tolerance / Q000187:drug effects
D019335:Nitroarginine; D009569:Nitric Oxide; C002385:linsidomine; D001120:Arginine; D008981:Molsidomine