Koritzinsky M, Wouters B G, Amellem O, Pettersen E O
Department of Cell Biology, The Norwegian Radium Hospital, Oslo.
Int J Radiat Biol. 2001 Mar;77(3):319-28. doi: 10.1080/09553000010019278.
To investigate cell cycle progression and radiation survival following prolonged hypoxia and re-oxygenation.
NHIK 3025 human cervical carcinoma cells were exposed to extremely hypoxic conditions (<4ppm O2) for 20 h and then re-oxygenated. The subsequent cell cycle progression was monitored by analysing cell cycle distribution at different time-points after re-oxygenation using two-dimensional flowcytometry. The clonogenic survival after a 3.6 Gy X-ray dose was also measured at each of these time-points. The measured radiation survival was compared with theoretical predictions based on cell cycle distribution and the radiation age response of the cells.
Following re-oxygenation the cells resumed cell cycle progression, completed S-phase, and then accumulated in G2. Non-clonogenic cells remained permanently arrested in G2, while the remainder of the cells completed mitosis after a few hours delay. The radiation survival of the hypoxia-pretreated cell population remained lower than for an exponentially growing control population for the investigated 50h of re-oxygenation. However, following 7 h of re-oxygenation, the radiation survival of the hypoxia-treated cell population correlated well with theoretically predicted values based on cell cycle distribution and radiation age response.
The work demonstrates that prolonged hypoxia followed by re-oxygenation results in a G2 delay similar to that observed after DNA damage. Furthermore, chronic hypoxia results in decreased radiation survival for at least 50h following the reintroduction of oxygen. The hypoxia-induced radiosensitization following 7 h of re-oxygenation could in large part be explained by the synchronous cell cycle progression that occurred.
研究长时间缺氧及复氧后的细胞周期进程和辐射存活情况。
将NHIK 3025人宫颈癌细胞置于极端缺氧条件（<4ppm O₂）下20小时，然后进行复氧。复氧后，通过二维流式细胞术分析不同时间点的细胞周期分布，监测后续细胞周期进程。在这些时间点的每一个，还测量了3.6 Gy X射线剂量后的克隆形成存活率。将测得的辐射存活率与基于细胞周期分布和细胞辐射年龄反应的理论预测值进行比较。
复氧后，细胞恢复细胞周期进程，完成S期，然后在G2期积累。非克隆形成细胞永久停滞在G2期，而其余细胞延迟数小时后完成有丝分裂。在复氧的50小时研究期间，缺氧预处理细胞群体的辐射存活率仍低于指数生长的对照群体。然而，复氧7小时后，缺氧处理细胞群体的辐射存活率与基于细胞周期分布和辐射年龄反应的理论预测值相关性良好。
该研究表明，长时间缺氧后复氧会导致类似于DNA损伤后观察到的G2期延迟。此外，慢性缺氧导致复氧后至少50小时辐射存活率降低。复氧7小时后缺氧诱导的放射增敏作用在很大程度上可以通过发生的同步细胞周期进程来解释。
