Temporal changes in PO2 of R3230AC tumors in Fischer-344 rats

Purpose: The purpose of this study was to characterize the kinetics of hypoxia-reoxygenation in a murine tumor. Information on the prevalence and kinetics of this process are lacking in solid tumors, although there are data on blood flow fluctuation. Materials and Methods: Oxygen tension (pO(2)) was monitored at one position in 1 cm diameter R3230Ac tumors of Fischer-344 rats, using 10-12 mu m diameter recessed-tip polarographic electrodes. Data were collected continuously at a sampling frequency of 25 Hz for 30-90 min. Mean arterial blood pressure (MAP) and heart rate were also monitored. Results: Temporal fluctuations in pO(2) were observed in all 13 experiments, To assess the potential for hypoxia-reoxygenation, two threshold pO(2) values were chosen (5 and 10 mmHg), and the number and duration of intervals that measurements resided below the thresholds was quantitated. In some experiments, the measurements did not fluctuate across the threshold values and, instead, either remained above or below them throughout the observation period. The percentage of sites: that did not fluctuate across the thresholds was 38 and 61% for the 10- and 5-mmHg values, respectively, For the remaining studies, fluctuations above and below the thresholds of hypoxia ranged around 4-7 events per h. There were wide variations in the duration of hypoxic episodes, ranging from less than 1 to more than 40 min. The percentage time that measurements were below the hypoxic thresholds was also variable, ranging from 30-90%. Conclusions: These results, taken with the already published data on temporal instability in human and murine tumor blood flow, suggest that intermittent hypoxia is a common phenomenon in tumors. Future studies will focus on the underlying mechanisms that contribute to this process, because it has important implications for radiation and chemotherapy and, perhaps, gene regulation in tumors. (C) 1998 Elsevier Science Inc.