Brurberg Kjetil G, Graff Bjørn A, Olsen Dag R, Rofstad Einar K
Group of Radiation Biology and Tumor Physiology, Department of Biophysics and Centre for Research and Training in Radiation Therapy, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
Int J Radiat Oncol Biol Phys. 2004 Feb 1;58(2):403-9. doi: 10.1016/j.ijrobp.2003.09.049.
A large number of studies have demonstrated that tumors are heterogeneous in oxygen tension (pO(2)) and may develop regions with chronically or acutely hypoxic cells during growth. In the present study, it was investigated whether experimental tumors of different lines may show characteristic pO(2) fluctuation patterns and hence may differ with respect to the kinetics of acute hypoxia.
A total of 70 xenografted tumors of two human melanoma lines (A-07 and R-18) were included in the study. Tissue pO(2) was measured simultaneously in two positions in each tumor for periods of at least 60 min using a two-channel fiberoptic oxygen-sensing device (OxyLite 2000, Oxford Optronix, Oxford, UK).
The mean pO(2) was calculated for each pO(2) trace, and this parameter was significantly greater in A-07 than in R-18 tumors (p <0.000001). Fluctuations in pO(2) around 3, 5, or 10 mm Hg were seen in a large fraction of the tumors of both lines. The pO(2) fluctuation frequency differed among individual traces from 0 to 20/h (A-07) and from 0 to 12/h (R-18) and was significantly greater in A-07 than in R-18 tumors (p = 0.0026). The absolute amplitude of the pO(2) fluctuations ranged from 1 to 16 mm Hg (A-07) and 1 to 33 mm Hg (R-18) and did not differ between the tumor lines. The relative amplitude was significantly higher in R-18 than in A-07 tumors (p <0.000001). The pO(2) values recorded simultaneously in the same tumor were in general not temporally coordinated.
Experimental tumors of different lines may show individual and characteristic pO(2) fluctuation patterns. The pO(2) fluctuations may result in regions with acutely hypoxic cells. The kinetics of the acute hypoxia may differ among tumors of different lines, individual tumors of the same line, and different regions within the same tumor.
大量研究表明,肿瘤在氧分压(pO₂)方面具有异质性,并且在生长过程中可能会出现含有慢性或急性缺氧细胞的区域。在本研究中,我们调查了不同品系的实验性肿瘤是否可能呈现出特征性的pO₂波动模式,从而在急性缺氧动力学方面存在差异。
本研究共纳入了70个移植了两种人类黑色素瘤细胞系(A - 07和R - 18)的肿瘤。使用双通道光纤氧传感装置(OxyLite 2000,Oxford Optronix,英国牛津),在每个肿瘤的两个位置同时测量组织pO₂,测量时间至少为60分钟。
计算每个pO₂轨迹的平均pO₂,该参数在A - 07肿瘤中显著高于R - 18肿瘤(p <0.000001)。在两个细胞系的大部分肿瘤中都观察到pO₂在3、5或10毫米汞柱左右波动。各个轨迹的pO₂波动频率在0至20次/小时(A - 07)和0至12次/小时(R - 18)之间有所不同,并且在A - 07肿瘤中显著高于R - 18肿瘤(p = 0.0026)。pO₂波动的绝对幅度范围为1至16毫米汞柱(A - 07)和1至33毫米汞柱(R - 18),在两个肿瘤细胞系之间没有差异。相对幅度在R - 18肿瘤中显著高于A - 07肿瘤(p <0.000001)。在同一肿瘤中同时记录的pO₂值通常在时间上没有协调性。
不同品系的实验性肿瘤可能呈现出个体特征性的pO₂波动模式。pO₂波动可能导致出现急性缺氧细胞区域。不同品系肿瘤、同品系的个体肿瘤以及同一肿瘤内的不同区域之间,急性缺氧的动力学可能存在差异。