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Tumor bioenergetics and blood flow in RIF-1 murine tumors treated with 5-fluorouracil

โœ Scribed by Shi-Jiang Li; Janna P. Wehrle; Jerry D. Glickson; Nirmal Kumar; Paul G. Braunschweiger


Publisher
John Wiley and Sons
Year
1991
Tongue
English
Weight
612 KB
Volume
22
Category
Article
ISSN
0740-3194

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โœฆ Synopsis


Abstract

Treatment of RIFโ€1 solid tumors with 5โ€fluorouracil (5โ€FU, 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 ^86^Rb^+^, was significantly increased after treatment with 5โ€FU, 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 5โ€FU. Perfusionโ€dependent ^86^Rb^+^ uptake returned to control levels by the 9th day after treatment with 100 mg/kg of 5โ€FU, but remained elevated on Days 9โ€“12 after the higher dose. By the lst day following treatment with 5โ€FU, in vivo ^31^P NMR spectra of treated tumors indicated significantly higher ratios of phosphocreatine to P~i~, higher pH, and lower ratios of P~i~ to nucleoside triphophates compared to untreated ageโ€matched controls. These changes persisted for 9 days following the lower 5โ€FU dose and for at least 12 days following the higher dose. Treatment with 5โ€FU induces profound, doseโ€dependent changes in tumor bioenergetics, which may result, at least in part, from changes in tumor perfusion after cytoreduction. ยฉ 1991 Academic Press, Inc.


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