Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina 29425, United States.
Chem Res Toxicol. 2023 Jul 17;36(7):983-1001. doi: 10.1021/acs.chemrestox.3c00045. Epub 2023 Jun 26.
Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of exposure to several aldehydes have been observed in numerous studies. At the molecular level, aldehydes damage DNA, cross-link DNA and proteins, lead to lipid peroxidation, and are associated with increased disease risk including cancer. People genetically predisposed to aldehyde sensitivity exhibit severe health outcomes. In various diseases such as Fanconi's anemia and Cockayne syndrome, loss of aldehyde-metabolizing pathways in conjunction with defects in DNA repair leads to widespread DNA damage. Importantly, aldehyde-associated mutagenicity is being explored in a growing number of studies, which could offer key insights into how they potentially contribute to tumorigenesis. Here, we review the genotoxic effects of various aldehydes, focusing particularly on the DNA adducts underlying the mutagenicity of environmentally derived aldehydes. We summarize the chemical structures of the aldehydes and their predominant DNA adducts, discuss various methodologies, and , commonly used in measuring aldehyde-associated mutagenesis, and highlight some recent studies looking at aldehyde-associated mutation signatures and spectra. We conclude the Review with a discussion on the challenges and future perspectives of investigating aldehyde-associated mutagenesis.
醛类广泛存在于环境中，有多种来源，如食物和饮料、工业废水、香烟烟雾和添加剂。许多研究已经观察到暴露于几种醛类物质会产生毒性作用。在分子水平上，醛类物质会破坏 DNA、交联 DNA 和蛋白质、导致脂质过氧化，并与增加的疾病风险（包括癌症）有关。对醛类敏感的遗传易感性人群表现出严重的健康后果。在范可尼贫血和 Cockayne 综合征等各种疾病中，醛代谢途径的丧失以及 DNA 修复缺陷导致广泛的 DNA 损伤。重要的是，越来越多的研究正在探索与醛类相关的致突变性，这可能为它们如何潜在促进肿瘤发生提供关键见解。在这里，我们综述了各种醛类的遗传毒性作用，特别关注环境衍生醛类致突变性的 DNA 加合物。我们总结了醛类的化学结构及其主要的 DNA 加合物，讨论了常用于测量与醛类相关的致突变性的各种方法，并强调了一些最近研究关注与醛类相关的突变特征和图谱。我们以讨论研究与醛类相关的致突变性的挑战和未来展望结束综述。
