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DNA 修复与炎症的相互作用及其与癌症的关联。

Interplay between DNA repair and inflammation, and the link to cancer.

机构信息

Departments of Therapeutic Radiology and Genetics .

出版信息

Crit Rev Biochem Mol Biol. 2014 Mar-Apr;49(2):116-39. doi: 10.3109/10409238.2013.875514. Epub 2014 Jan 13.

Abstract

DNA damage and repair are linked to cancer. DNA damage that is induced endogenously or from exogenous sources has the potential to result in mutations and genomic instability if not properly repaired, eventually leading to cancer. Inflammation is also linked to cancer. Reactive oxygen and nitrogen species (RONs) produced by inflammatory cells at sites of infection can induce DNA damage. RONs can also amplify inflammatory responses, leading to increased DNA damage. Here, we focus on the links between DNA damage, repair, and inflammation, as they relate to cancer. We examine the interplay between chronic inflammation, DNA damage and repair and review recent findings in this rapidly emerging field, including the links between DNA damage and the innate immune system, and the roles of inflammation in altering the microbiome, which subsequently leads to the induction of DNA damage in the colon. Mouse models of defective DNA repair and inflammatory control are extensively reviewed, including treatment of mouse models with pathogens, which leads to DNA damage. The roles of microRNAs in regulating inflammation and DNA repair are discussed. Importantly, DNA repair and inflammation are linked in many important ways, and in some cases balance each other to maintain homeostasis. The failure to repair DNA damage or to control inflammatory responses has the potential to lead to cancer.

摘要

DNA 损伤与修复与癌症有关。如果不能正确修复,由内源性或外源性因素诱导的 DNA 损伤有可能导致突变和基因组不稳定,最终导致癌症。炎症也与癌症有关。感染部位炎症细胞产生的活性氧和氮物种(RONs)会诱导 DNA 损伤。RONs 还可以放大炎症反应,导致更多的 DNA 损伤。在这里,我们重点关注 DNA 损伤、修复和炎症之间的联系,因为它们与癌症有关。我们检查了慢性炎症、DNA 损伤和修复之间的相互作用,并回顾了这一快速发展领域的最新发现,包括 DNA 损伤与先天免疫系统之间的联系,以及炎症在改变微生物组中的作用,从而导致结肠中 DNA 损伤的诱导。我们广泛审查了 DNA 修复和炎症控制有缺陷的小鼠模型,包括用病原体治疗小鼠模型,这会导致 DNA 损伤。还讨论了 microRNAs 在调节炎症和 DNA 修复中的作用。重要的是,DNA 修复和炎症以多种重要方式相互关联,在某些情况下,它们相互平衡以维持体内平衡。不能修复 DNA 损伤或控制炎症反应有可能导致癌症。

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