Abstract:
Radiation cytogenetics has a rich history seldom appreciated by those outside the field. Early radiobiology was dominated by physics and biophysical concepts that borrowed heavily from the study of radiation-induced chromosome aberrations. From such studies, quantitative relationships between biological effect and changes in absorbed dose, dose rate and ionization density were codified into key concepts of radiobiological theory that have persisted for nearly a century. This review aims to provide a historical perspective of some of these concepts, including evidence supporting the contention that chromosome aberrations underlie development of many, if not most, of the biological effects of concern for humans exposed to ionizing radiations including cancer induction, on the one hand, and tumor eradication on the other. The significance of discoveries originating from these studies has widened and extended far beyond their original scope. Chromosome structural rearrangements viewed in mitotic cells were first attributed to the production of breaks by the radiations during interphase, followed by the rejoining or mis-rejoining among ends of other nearby breaks. These relatively modest beginnings eventually led to the discovery and characterization of DNA repair of double-strand breaks by non-homologous end joining, whose importance to various biological processes is now widely appreciated. Two examples, among many, are V(D)J recombination and speciation. Rapid technological advancements in cytogenetics, the burgeoning fields of molecular radiobiology and third-generation sequencing served as a point of confluence between the old and new. As a result, the emergent field of \"cytogenomics\" now becomes uniquely positioned for the purpose of more fully understanding mechanisms underlying the biological effects of ionizing radiation exposure.
摘要:
辐射细胞遗传学具有丰富的历史,很少被领域外的人欣赏。早期的放射生物学由物理学和生物物理概念主导,这些概念大量借鉴了辐射诱导的染色体畸变的研究。从这些研究中,生物效应与吸收剂量变化之间的定量关系,剂量率和电离密度被编码为放射生物学理论的关键概念,这些概念已经持续了近一个世纪。这篇综述旨在提供其中一些概念的历史视角,包括支持染色体畸变是许多发育的基础的论点的证据,如果不是大多数,对暴露于电离辐射包括癌症诱导的人类的生物效应的关注,一方面,另一个是肿瘤根除。源自这些研究的发现的意义已经远远超出了它们最初的范围。在有丝分裂细胞中观察到的染色体结构重排首先归因于间期辐射产生的断裂,随后是其他附近休息的末端之间的重新连接或错误连接。这些相对温和的开始最终导致了通过非同源末端连接对双链断裂的DNA修复的发现和表征,它对各种生物过程的重要性现在得到了广泛的重视。两个例子,在许多人中,是V(D)J重组和形态形成。细胞遗传学的快速技术进步,分子放射生物学和第三代测序的新兴领域是新旧之间的汇合点。因此,“细胞基因组学”的新兴领域现在变得独特,目的是更全面地理解电离辐射暴露的生物学效应的潜在机制。