Abstract

DNA damaging agents have been a cornerstone of cancer therapy for nearly a century. The discovery of many of these chemicals, particularly the alkylating agents, are deeply entwined with the development of poisonous materials originally intended for use in warfare. Over the last decades, their anti-proliferative effects have focused on the specific mechanisms by which they damage DNA, and the factors involved in the repair of such damage. Due to the variety of aberrant adducts created even for the simplest alkylating agents, numerous pathways of repair are engaged as a defense against this damage. More recent work has underscored the role of RNA damage in the cellular response to these agents, although the understanding of their role in relation to established DNA repair pathways is still in its infancy. In this review, we discuss the chemistry of alkylating agents, the numerous ways in which they damage nucleic acids, as well as the specific DNA and RNA repair pathways which are engaged to counter their effects.

摘要

近一个世纪以来，DNA 损伤剂一直是癌症治疗的基石。许多这些化学物质的发现，特别是烷化剂，与最初用于战争的有毒材料的开发密切相关。在过去的几十年里，它们的抗增殖作用主要集中在它们破坏 DNA 的具体机制，以及参与修复这种损伤的因素上。由于即使对于最简单的烷化剂也会产生多种异常加合物，因此许多修复途径都被用于防御这种损伤。最近的工作强调了 RNA 损伤在细胞对这些药物的反应中的作用，尽管对它们与已建立的 DNA 修复途径相关的作用的理解仍处于起步阶段。在本次审查中，