School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
Collage of Pharmacy, Department of Pharmacology, Dalian Medical University, Dalian 116044, China; State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
Mutat Res. 2024 Jul-Dec;829:111883. doi: 10.1016/j.mrfmmm.2024.111883. Epub 2024 Sep 11.
The integrity of the genetic material in human cells is continuously challenged by environmental agents and endogenous stresses. Among these, environmental carcinogens are pivotal in initiating complex DNA lesions that can lead to malignant transformations if not properly repaired. This review synthesizes current knowledge on the molecular dynamics of DNA repair mechanisms and their interplay with various environmental carcinogens, providing a comprehensive overview of how these interactions contribute to cancer initiation and progression. We examine key DNA repair pathways including base excision repair, nucleotide excision repair, and double-strand break repair and their regulatory networks, highlighting how defects in these pathways can exacerbate carcinogen-induced damage. Further, we discuss how understanding these molecular interactions offers novel insights into potential therapeutic strategies. This includes leveraging synthetic lethality concepts and designing targeted therapies that exploit specific DNA repair vulnerabilities in cancer cells. By integrating recent advances in molecular biology, genetics, and oncology, this review aims to illuminate the complex landscape of DNA repair and carcinogen-induced carcinogenesis, setting the stage for future research and therapeutic innovations.
人类细胞中的遗传物质完整性不断受到环境因素和内源性应激的挑战。在这些因素中，环境致癌物在引发复杂的 DNA 损伤方面起着关键作用，如果不能得到妥善修复，这些损伤可能导致恶性转化。本综述综合了当前关于 DNA 修复机制的分子动力学及其与各种环境致癌物相互作用的知识，全面概述了这些相互作用如何促进癌症的发生和发展。我们研究了包括碱基切除修复、核苷酸切除修复和双链断裂修复在内的关键 DNA 修复途径及其调控网络，强调了这些途径中的缺陷如何加剧致癌剂诱导的损伤。此外，我们还讨论了如何理解这些分子相互作用为潜在的治疗策略提供新的见解。这包括利用合成致死性概念和设计靶向治疗，利用癌细胞中特定的 DNA 修复脆弱性。通过整合分子生物学、遗传学和肿瘤学的最新进展，本综述旨在阐明 DNA 修复和致癌物诱导的致癌作用的复杂景观，为未来的研究和治疗创新奠定基础。
