31P-nuclear magnetic resonance studies of the effect of recombinant human interleukin 1 alpha on the bioenergetics of RIF-1 tumors.
The effect of a single injection of human recombinant interleukin 1 alpha (IL-1 alpha) on s.c. RIF-1 tumors in mice was studied by in vivo 31P nuclear magnetic resonance spectroscopy. Spectra were obtained before and up to 24 h after IL-1 alpha. At 2, 4, 6, and 8 h after IL-1 alpha injection, RIF-1 tumors exhibited a reduction in bioenergetic status compared to untreated controls. The Pi to beta-nucleoside triphosphate and the phosphomonoester to beta-nucleoside triphosphate ratios increased, while the phosphocreatine to Pi and phosphodiester to phosphomonoester ratios decreased. Tumor blood flow, estimated by 86RbCl uptake, decreased within 30 min after IL-1 alpha treatment. Minimum perfusion was detected at 4 h, with recovery between 6 and 12 h after IL-1 alpha treatment. Histological sections of the RIF-1 tumors revealed intravascular congestion by 2 h, extravascular hemorrhage by 4 h, and necrosis by 12 h after treatment with IL-1 alpha. The time course of bioenergetic changes in RIF-1 tumors determined by 31P-NMR spectroscopy was found to parallel the reduction and subsequent recovery of tumor blood flow.
Constantinidis
I
I
Johns Hopkins University, School of Medicine, Department of Radiology, Baltimore, Maryland 21205.
Braunschweiger
P G
PG
Wehrle
J P
JP
Kumar
N
N
Johnson
C S
CS
Furmanski
P
P
Glickson
J D
JD
D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D009711:Nucleotides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D010758:Phosphorus; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology
D007375:Interleukin-1; D009711:Nucleotides; D010710:Phosphates; D011994:Recombinant Proteins; D010725:Phosphocreatine; D010758:Phosphorus