Fourier analysis of fluctuations of oxygen tension and blood flow in R3230Ac tumors and muscle in rats
Tumor hypoxia is a major barrier to tumor radiation therapy. Typically tumor hypoxia occurs in two forms: chronic and acute. Although the existence of acute hypoxia has long been acknowledged, its temporal characteristics have never been directly measured and documented. In this study tumor PO2, blood flow (BF), and arterial blood pressure (BP) were measured simultaneously in nine Fischer 344 rats bearing R3230Ac rat mammary adenocarcinomas in the subcutis of the left hindleg. We measured PO2 at a single location for 36-125 min using recessed-tip oxygen microelectrodes. Simultaneously, we measured tumor BF at two sites within the tumor using laser-Doppler flowmetry (LDF). Similar recordings were made in the quadriceps muscle of seven non-tumor-bearing rats. The PO2, tumor BF, and BP records were subjected to Fourier analysis. PO2 and BF showed low-frequency fluctuations (<2 cycles/min) in both tumor and muscle, but the magnitude of the changes in tumor was greater. Tumor BF showed more activity at low frequencies than muscle BF, and the magnitude tended to be greater. No strong correlations were found between PO2 and BF power spectra for either tumor or muscle or between the frequency patterns of BP and tumor PO2 spectra. These results quantitatively demonstrate, for the first time, that BF and PO2 fluctuate at very low frequencies in tumors. In addition to having biological significance for tumor therapy, these fluctuations may have the potential to alter tumor cell behavior via induction of hypoxia reoxygenation injury and/or altered gene expression.
Braun, RD; Lanzen, JL; Dewhirst, MW
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