Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana.
Cancer Res. 2022 Dec 2;82(23):4313-4321. doi: 10.1158/0008-5472.CAN-22-2311.
Oxygen (O2) plays a key role in cellular homeostasis. O2 levels are tightly regulated in vivo such that each tissue receives an optimal amount to maintain physiologic status. Physiologic O2 levels in various organs range between 2% and 9% in vivo, with the highest levels of 9% in the kidneys and the lowest of 0.5% in parts of the brain. This physiologic range of O2 tensions is disrupted in pathologic conditions such as cancer, where it can reach as low as 0.5%. Regardless of the state, O2 tension in vivo is maintained at significantly lower levels than ambient O2, which is approximately 21%. Yet, routine in vitro cellular manipulations are carried out in ambient air, regardless of whether or not they are eventually transferred to hypoxic conditions for subsequent studies. Even brief exposure of hematopoietic stem cells to ambient air can cause detrimental effects through a mechanism termed extraphysiologic oxygen shock/stress (EPHOSS), leading to reduced engraftment capabilities. Here, we provide an overview of the effects of ambient air exposure on stem and non-stem cell subtypes, with a focus on recent findings that reveal the impact of EPHOSS on cancer cells.
氧气（O2）在细胞内稳态中起着关键作用。在体内，O2 水平受到严格调节，以使每个组织获得维持生理状态的最佳量。各种器官的生理 O2 水平在体内范围为 2%至 9%，其中肾脏的 O2 水平最高为 9%，而大脑的某些部位的 O2 水平最低为 0.5%。在癌症等病理条件下，这种 O2 张力的生理范围会被打破，其 O2 水平可低至 0.5%。无论状态如何，体内 O2 张力都保持在明显低于环境 O2 的水平，环境 O2 约为 21%。然而，常规的体外细胞操作都是在环境空气中进行的，无论它们最终是否被转移到缺氧条件下进行后续研究。即使短暂暴露于环境空气中也会通过一种称为“超生理氧冲击/应激（EPHOSS）”的机制对造血干细胞造成有害影响，从而降低其植入能力。在这里，我们概述了环境空气暴露对干细胞和非干细胞亚型的影响，重点介绍了最近的发现，这些发现揭示了 EPHOSS 对癌细胞的影响。
