Radiation Biophysics and Radiobiology Group, Physics Department, University of Pavia, Pavia, Italy.
Institute for Radiation Medicine, Helmholtz Centre Munich, Munich, Germany.
Radiat Environ Biophys. 2022 Nov;61(4):545-559. doi: 10.1007/s00411-022-00989-z. Epub 2022 Oct 12.
The outcome of the exposure of living organisms to ionizing radiation is determined by the distribution of the associated energy deposition at different spatial scales. Radiation proceeds through ionizations and excitations of hit molecules with an ~ nm spacing. Approaches such as nanodosimetry/microdosimetry and Monte Carlo track-structure simulations have been successfully adopted to investigate radiation quality effects: they allow to explore correlations between the spatial clustering of such energy depositions at the scales of DNA or chromosome domains and their biological consequences at the cellular level. Physical features alone, however, are not enough to assess the entity and complexity of radiation-induced DNA damage: this latter is the result of an interplay between radiation track structure and the spatial architecture of chromatin, and further depends on the chromatin dynamic response, affecting the activation and efficiency of the repair machinery. The heterogeneity of radiation energy depositions at the single-cell level affects the trade-off between cell inactivation and induction of viable mutations and hence influences radiation-induced carcinogenesis. In radiation therapy, where the goal is cancer cell inactivation, the delivery of a homogenous dose to the tumour has been the traditional approach in clinical practice. However, evidence is accumulating that introducing heterogeneity with spatially fractionated beams (mini- and microbeam therapy) can lead to significant advantages, particularly in sparing normal tissues. Such findings cannot be explained in merely physical terms, and their interpretation requires considering the scales at play in the underlying biological mechanisms, suggesting a systemic response to radiation.
生物体暴露于电离辐射的结果取决于不同空间尺度上相关能量沉积的分布。辐射通过与~nm 间隔的命中分子的电离和激发来进行。纳米剂量学/微剂量学和蒙特卡罗轨迹结构模拟等方法已成功用于研究辐射质量效应：它们允许探索这种能量沉积在 DNA 或染色体域尺度上的空间聚类与其在细胞水平上的生物学后果之间的相关性。然而，仅物理特征不足以评估辐射诱导 DNA 损伤的实体和复杂性：后者是辐射轨迹结构与染色质空间结构之间相互作用的结果，并且进一步取决于染色质动态响应，影响修复机制的激活和效率。单细胞水平上辐射能量沉积的异质性影响细胞失活与诱导存活突变之间的权衡，从而影响辐射诱导的致癌作用。在放射治疗中，其目的是使癌细胞失活，向肿瘤提供均匀剂量一直是临床实践中的传统方法。然而，越来越多的证据表明，引入具有空间分割束（微束和微束治疗）的异质性可以带来显著的优势，特别是在保护正常组织方面。这些发现不能仅用物理术语来解释，其解释需要考虑在潜在生物学机制中起作用的尺度，这表明对辐射的系统反应。
