Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing
Tumor-dependent kinetics of partial pressure of oxygen fluctuations during air and oxygen breathing
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DOI：
10.1158/0008-5472.can-03-0947
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发表时间：
2004-09-01
期刊：
影响因子：
11.2
通讯作者：
Dewhirst, MW
中科院分区：
文献类型：
--
作者：
C치rdenas-Navia, LI;Yu, DH;Dewhirst, MW
本研究的主要目的是研究在空气和氧气呼吸条件下纤维肉瘤（FSA）和9 L肿瘤中氧分压（pO（2））波动的动力学。总的假设是，与氧张力波动相关的关键因素在两种肿瘤类型之间会有所不同，并且是呼吸气体中氧含量的函数。为了帮助解释时间数据，测量了移植到Nembutal麻醉（50 mg/kg）Fischer 344大鼠后腿皮下组织中的10个FSA和8个9 L肿瘤的空间pO（2）分布。在肿瘤中插入尖端凹陷的氧微电极，沿着沿着3 mm的路径以50 μ m的步长记录线性pO（2）测量值，同时通过股动脉通路测量血压。此外，在FSA（n = 11）或9 L肿瘤（n = 12）中，在单个位置测量pO（2）90至120分钟。45分钟后，大鼠从空气呼吸转换为100%O-2呼吸。通过评估时间pO（2）记录超过10 mm Hg阈值的次数，评价其潜在的放射生物学意义。此外，对空气和O-2呼吸的数据进行傅立叶分析。FSA和9 L肿瘤的空间中位pO（2）测量值分别为4和1 mm Hg。9 L组pO（2）低于或等于2.5 mm Hg的患者多于FSA组，而在2.5 ~ 10 mm Hg之间则相反。FSA和9 L肿瘤中的匹莫硝唑染色模式支持这些结果。在空气和O-2呼吸期间，在所有实验中观察到时间pO（2）不稳定性。阈值分析表明，10 mm Hg阈值每小时跨越2 - 5次，与肿瘤类型无关。然而，9 L pO（2）波动的幅度约为FSA波动的8倍，如傅立叶变换分析所评估的（Wilcoxon，P < 0.005）。氧呼吸显著增加FSA的pO（2）中位数，从3到8 mm Hg（P < 0.005），并导致pO（2）波动的频率和幅度显著增加。100%氧气呼吸对9 L肿瘤pO（2）没有影响，但它降低了pO（2）波动的幅度，具有临界意义。这些结果表明，这两种肿瘤在空气和O-2呼吸下的空间和时间氧合条件方面存在显着差异。本文报道的pO（2）波动类型预计会显著影响放疗反应，并可能是遗传不稳定性、血管生成增加和转移的来源。
The primary purpose of this study was to examine the kinetics of partial pressure of oxygen (pO(2)) fluctuations in fibrosarcoma (FSA) and 9L tumors under air and O-2 breathing conditions. The overall hypothesis was that key factors relating to oxygen tension fluctuations would vary between the two tumor types and as a function of the oxygen content of the breathing gas. To assist in the interpretation of the temporal data, spatial pO(2) distributions were measured in 10 FSA and 8 9L tumors transplanted into the subcutis of the hind leg of Nembutal-anesthetized (50 mg/kg) Fischer 344 rats. Recessed-tip oxygen microelectrodes were inserted into the tumor, and linear pO(2) measurements were recorded in 50mum steps along a 3-mm path, and blood pressure was simultaneously measured via femoral arterial access. Additionally, pO(2) was measured at a single location for 90 to 120 minutes in FSA (n = 11) or 9L tumors (n = 12). Rats were switched from air to 100% O-2 breathing after 45 minutes. Temporal pO(2) records were evaluated for their potential radiobiological significance by assessing the number of times they crossed a 10-mm-Hg threshold. In addition, the data were subjected to Fourier analysis for air and O-2 breathing. FSA and 9L tumors had spatial median pO(2) measurements of 4 and I mm Hg, respectively. 9L had more low pO(2) measurements less than or equal to2.5 mm Hg than did FSA, whereas between 2.5 and 10 mm Hg this pattern was reversed. Pimonidazole staining patterns in FSA and 9L tumors supported these results. Temporal pO(2) instability was observed in all experiments during air and O-2 breathing. Threshold analyses indicated that the 10 mm Hg threshold was crossed 2 to 5 times per hour, independent of tumor type. However, the magnitude of 9L pO(2) fluctuations was approximately eight times greater than FSA fluctuations, as assessed with Fourier transform analysis (Wilcoxon, P < 0.005). O-2 breathing significantly increased median pO(2) in FSA from 3 to 8 mm Hg (P < 0.005) and caused a significant increase in frequency and magnitude of pO(2) fluctuations. One hundred percent O-2 breathing had no effect on 9L tumor pO(2), and it decreased the magnitude of pO(2) fluctuations with borderline significance. These results show that these two tumors differ significantly with respect to spatial and temporal oxygenation conditions under air and O-2 breathing. Fluctuations of pO(2) of the type reported herein are predicted to significantly affect radiotherapy response and could be a source for genetic instability, increased angiogenesis, and metastases.