Dewhirst M W, Braun R D, Lanzen J L
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Radiat Oncol Biol Phys. 1998 Nov 1;42(4):723-6. doi: 10.1016/s0360-3016(98)00304-6.
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.
Oxygen tension (pO2) was monitored at one position in 1 cm diameter R3230Ac tumors of Fischer-344 rats, using 10-12 microm 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.
Temporal fluctuations in pO2 were observed in all 13 experiments. To assess the potential for hypoxia-reoxygenation, two threshold pO2 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%.
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.
本研究旨在描述小鼠肿瘤中缺氧-复氧的动力学特征。尽管有关于血流波动的数据，但实体瘤中该过程的发生率和动力学信息尚缺乏。
使用直径为10 - 12微米的凹尖极谱电极，在Fischer - 344大鼠直径1厘米的R3230Ac肿瘤的一个位置监测氧张力（pO2）。以25赫兹的采样频率连续收集数据30 - 90分钟。同时监测平均动脉血压（MAP）和心率。
在所有13项实验中均观察到pO2的时间波动。为评估缺氧-复氧的可能性，选择了两个pO2阈值（5和10毫米汞柱），并对测量值低于阈值的间隔次数和持续时间进行了定量。在一些实验中，测量值未跨越阈值波动，而是在整个观察期内要么保持高于阈值，要么低于阈值。对于10毫米汞柱和5毫米汞柱的值，未跨越阈值波动的位点百分比分别为38%和61%。对于其余研究，缺氧阈值上下的波动约为每小时4 - 7次。缺氧发作的持续时间差异很大，从不到1分钟到超过40分钟不等。测量值低于缺氧阈值的时间百分比也各不相同，范围为30% - 90%。
这些结果与已发表的关于人和小鼠肿瘤血流时间不稳定性的数据表明，间歇性缺氧是肿瘤中的常见现象。未来的研究将聚焦于促成这一过程的潜在机制，因为它对肿瘤的放疗和化疗以及可能的基因调控具有重要意义。
