Durand R E
Adv Exp Med Biol. 1983;159:419-34. doi: 10.1007/978-1-4684-7790-0_36.
Chinese hamster V-79-171 cells, when placed in stirred suspension cultures, spontaneously grow as spherical multicell aggregates (spheroids) which eventually contain many thousand tightly-packed cells. These spheroids thus provide a valuable model for the study of oxygen transport, since oxygen concentration at the spheroid periphery can be fairly precisely controlled in the stirred suspension, and the consequences of oxygen diffusion inward through the tissue-like mass can be determined experimentally and compared with theoretical calculations. As in human tumors, appearance of central necrosis can be correlated with severe hypoxia. Additionally, since severely hypoxic cells are considerably more resistant to radiation than are oxygenated cells, determination of the fraction of hypoxic cells by their radioresistance provides a noninvasive technique for monitoring respiratory processes. Using this approach, we have found an excellent correlation between the rate of cellular oxygen utilization by a single cell suspension and the net radio-sensitivity of multicell spheroids when treated with modulating agents, varying from direct control of metabolic activity by changing the ambient temperature, to less direct effects on cellular oxygen consumption induced by exposure of cells to nitroheterocyclic radiosensitizers, chemotherapeutic agents, anesthetics, antibiotics, and even cell growth factors including insulin. Our data from these studies indicate that, at least in the simplistic spheroid system where oxygen delivery to the internal cells is a direct function of the respiratory activity of the external cells, control of cellular oxygen utilization is a convenient and effective method of controlling the net radiosensitivity.
中国仓鼠V - 79 - 171细胞置于搅拌悬浮培养中时，会自发生长成球形多细胞聚集体（球体），最终包含数千个紧密堆积的细胞。因此，这些球体为研究氧转运提供了一个有价值的模型，因为在搅拌悬浮液中可以相当精确地控制球体周边的氧浓度，并且可以通过实验确定氧向内扩散穿过类组织团块的后果，并与理论计算进行比较。与人类肿瘤一样，中央坏死的出现与严重缺氧相关。此外，由于严重缺氧的细胞比含氧细胞对辐射的抵抗力强得多，通过其放射抗性确定缺氧细胞的比例提供了一种监测呼吸过程的非侵入性技术。使用这种方法，我们发现，当用调节剂处理时，单细胞悬浮液的细胞氧利用速率与多细胞球体的净放射敏感性之间存在极好的相关性，这些调节剂从通过改变环境温度直接控制代谢活性到对细胞氧消耗的较间接影响，后者是由细胞暴露于硝基杂环放射增敏剂、化疗药物、麻醉剂、抗生素甚至包括胰岛素在内的细胞生长因子引起的。我们这些研究的数据表明，至少在简单的球体系统中，其中向内部细胞的氧输送是外部细胞呼吸活性的直接函数，控制细胞氧利用是控制净放射敏感性的一种方便有效的方法。
