Oxidative stress is universal to all cell types, including cancer. It is elicited by a surplus of reactive oxygen species (ROS) or a reduced cellular ability to defend against those. At low levels (oxidative eustress), this induces altered cellular signaling, while at higher levels (oxidative distress), cellular toxicity and non-specific redox signaling become apparent. While oxidation-induced cell death is a hallmark of many cancer therapies, including ROS-producing radiotherapy, some chemotherapies and targeted therapies, photodynamic therapy, and recently emerging physical modalities such as medical gas plasma (a multi-ROS generating technology), less is known about the transcriptional profiles predisposing cancer cells to oxidative demise. In particular, which genes are associated with resistance or sensitivity to ROS overload and subsequent toxicity has not been systematically investigated. Moreover, it is unclear if there are differences between oxidant types, such as hydrogen peroxide and hypochlorous acid. To this end, we here employed 35 cell lines of various origins (e.g., adenocarcinoma, melanoma, leukemia, squamous cell carcinoma, and neuroblastoma). We first performed in-house transcriptomic analysis to assess baseline transcriptional profiles. Second, all cell lines were exposed to four different ROS concentrations of either hydrogen peroxide, hypochlorous, or gas plasma exposure. Third, correlation analysis was performed to identify genes associated with (i) oxidative stress sensitivity, (ii) oxidative stress resistance, and (iii) similarities and/or differences between the different oxidative stress inducers. Intriguingly, distinct gene sets were found for all treatments, and there was a striking difference between hydrogen peroxide and hypochlorous acid, suggesting different modes of action of both oxidants.
氧化应激是所有细胞类型（包括癌细胞）普遍存在的现象，它由活性氧（ROS）过量或细胞防御能力降低所引发。在低水平（氧化良性应激）下，这会引发细胞信号传导的改变；而在较高水平（氧化恶性应激）下，细胞毒性和非特异性氧化还原信号传导变得明显。虽然氧化诱导的细胞死亡是许多癌症疗法的标志，包括产生ROS的放射治疗、某些化疗和靶向治疗、光动力疗法以及最近出现的物理疗法（如医用气体等离子体，一种多ROS生成技术），但对于使癌细胞易于发生氧化死亡的转录谱知之甚少。特别是，哪些基因与对ROS过载及后续毒性的抵抗性或敏感性相关，尚未得到系统研究。此外，尚不清楚不同氧化剂类型（如过氧化氢和次氯酸）之间是否存在差异。为此，我们使用了35种不同来源的细胞系（例如腺癌、黑色素瘤、白血病、鳞状细胞癌和神经母细胞瘤）。首先，我们进行了内部转录组分析以评估基线转录谱。其次，将所有细胞系暴露于四种不同浓度的过氧化氢、次氯酸或气体等离子体产生的ROS中。第三，进行相关性分析以识别与（i）氧化应激敏感性、（ii）氧化应激抵抗性以及（iii）不同氧化应激诱导剂之间的相似性和/或差异相关的基因。有趣的是，所有处理都发现了不同的基因集，并且过氧化氢和次氯酸之间存在显著差异，这表明两种氧化剂的作用模式不同。
肿瘤(癌症)患者之家