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

DNA破坏剂已成为癌症治疗近一个世纪的基石。这些化学物质，特别是烷基化剂的发现，与最初用于战争的有毒物质的发展紧密地联系在一起。在过去的几十年中，它们的抗增殖作用集中在它们破坏DNA的特定机制上，以及修复这种破坏所涉及的因素。由于即使是最简单的烷基化剂，也会产生各种异常的加合物，因此采用了多种修复途径来防御这种损害。尽管对它们与已建立的DNA修复途径有关的作用的了解仍处于起步阶段，但最近的工作强调了RNA损伤在细胞对这些药物的反应中的作用。在这篇评论中