ABSTRACT Water is the major constituent of the human body and plays a vital role in biochemical processes. Even subtle variations in the structure or dynamics of intracellular water may be the driving force for disrupting homeostasis in the highly crowded intracellular milieu, which in turn may trigger biomolecular dysfunction eventually leading to cell death. This article highlights several studies on human cells and DNA, that establish intracellular water as a key mediator of cytotoxicity. Inelastic and quasi-elastic neutron scattering techniques were applied, which provide a direct probe, at the atomic scale, of the behaviour of both cytoplasmic and hydration water, in the presence and absence of drugs. While the primary targets of drugs are biological receptors, we propose water as a potential secondary target for chemotherapy. The methodology presented constitutes an innovative approach for chemotherapeutic research. In addition, it showcases the value of neutron spectroscopy, a traditionally physico-chemical tool, for clinically-relevant research.

中文翻译：

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细胞内水作为抗癌药物作用的介质

摘要 水是人体的主要成分，在生物化学过程中起着至关重要的作用。即使细胞内水的结构或动力学的细微变化也可能是破坏高度拥挤的细胞内环境中稳态的驱动力，这反过来又可能引发生物分子功能障碍，最终导致细胞死亡。本文重点介绍了几项关于人类细胞和 DNA 的研究，这些研究将细胞内水作为细胞毒性的关键介质。应用了非弹性和准弹性中子散射技术，它们在原子尺度上直接探测细胞质和水合水在药物存在和不存在的情况下的行为。虽然药物的主要靶点是生物受体，但我们建议将水作为化疗的潜在次要靶点。所提出的方法构成了化学治疗研究的创新方法。此外，它还展示了中子能谱（一种传统的物理化学工具）在临床相关研究中的价值。