Ozone is used to treat several medical conditions, while the underlying mechanisms of action are sometimes poorly understood. In the current study, we exposed cultured human epithelial (HeLa) cells acutely and repeatedly to ozone and investigated the effects thereof on cell viability. The involvement of anti-apoptotic pathways in observed adaptive responses to ozone were investigated by employing the Akt inhibitor (-)-deguelin. Cells were exposed to an ozone-saturated physiological solution using various dosing regimens, including acute exposure and various repetitive exposures. Cell viability was determined with Trypan Blue or MTT tests, or by a DNA-fragmentation (comet) assay. Acute ozone exposure compromised cell membrane integrity severely, while adaptation to reverse an initial reduction in mitochondrial activity was observed. Repetitive, short-duration exposures followed by a single long-duration exposure to ozone furnished a protective adaptation that was reversed by Akt inhibition. Extracellular and intracellular damage (and adaptation) occurs differentially. While acute ozone may decrease cell viability, multiple preexposures up-regulates cellular plasticity via induction of anti-apoptotic pathways in a treatment regimen-specific manner.

中文翻译：

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在培养的人上皮（HeLa）细胞中，急性和反复暴露于臭氧后的细胞弹性和适应性研究。

臭氧可用于治疗多种疾病，但有时对其潜在的作用机理了解甚少。在当前的研究中，我们将培养的人类上皮细胞（HeLa）急性反复暴露于臭氧中，并研究了其对细胞活力的影响。通过使用Akt抑制剂（-）-deguelin，研究了抗凋亡途径在观察到的对臭氧的适应性反应中的作用。使用各种给药方案，包括急性暴露和各种重复暴露，将细胞暴露于臭氧饱和的生理溶液中。用锥虫蓝或MTT试验或通过DNA片段化（彗星）试验确定细胞活力。急性臭氧暴露严重损害了细胞膜的完整性，同时观察到可以逆转线粒体活性的最初降低。重复的 短期暴露后再长期暴露于臭氧中，提供了保护性适应，但被Akt抑制所逆转。细胞外和细胞内损伤（和适应性）的发生差异。尽管急性臭氧可能会降低细胞活力，但多次预暴露会通过以治疗方案特异性方式诱导抗凋亡途径来上调细胞可塑性。