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Tumor bioenergetics and blood flow in RIFâ1 murine tumors treated with 5âfluorouracil
Treatment of RIFâ1 solid tumors with 5âfluorouracil (5âFU, 100 or 200 mg/kg, ip) caused substantial regression of the tumors, with regrowth initiated on Day 6 (100 mg/kg) or Day 9 (200 mg/kg). Blood perfusion in the tumor, estimated by uptake of 86Rb+, was significantly increased after treatment with 5âFU, while Rb+ uptake in normal tissues (skin, muscle) was unaffected. The increase in tumor perfusion during the first few days following treatment was significantly greater in animals treated with the higher dose of 5âFU. Perfusionâdependent 86Rb+ uptake returned to control levels by the 9th day after treatment with 100 mg/kg of 5âFU, but remained elevated on Days 9â12 after the higher dose. By the lst day following treatment with 5âFU, in vivo 31P NMR spectra of treated tumors indicated significantly higher ratios of phosphocreatine to Pi, higher pH, and lower ratios of Pi to nucleoside triphophates compared to untreated ageâmatched controls. These changes persisted for 9 days following the lower 5âFU dose and for at least 12 days following the higher dose. Treatment with 5âFU induces profound, doseâdependent changes in tumor bioenergetics, which may result, at least in part, from changes in tumor perfusion after cytoreduction. © 1991 Academic Press, Inc