The effect of a single injection of human recombinant interleukin 1α (IL-1α) on s.c. RIF-1 tumors in mice was studied by in vivo31P nuclear magnetic resonance spectroscopy. Spectra were obtained before and up to 24 h after IL-1α. At 2, 4, 6, and 8 h after IL-1α injection, RIF-1 tumors exhibited a reduction in bioenergetic status compared to untreated controls. The P1 to β-nucleoside triphosphate and the phosphomonoester to β-nucleoside triphosphate ratios increased, while the phosphocreatine to P1 and phosphodiester to phosphomonoester ratios decreased. Tumor blood flow, estimated by 86RbCl uptake, decreased within 30 min after IL-1α treatment. Minimum perfusion was detected at 4 h, with recovery between 6 and 12 h after IL-1α 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-1α. 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.

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This work has been supported in part by NIH Grants P01-CA44703, R01-CA48077, -CA33188 and a gift to AMC Cancer Research Center from The McDonnell Douglas Foundation.

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