School of Public Health, Indiana University, Bloomington, Indiana.
Curr Pharm Des. 2018;24(40):4771-4778. doi: 10.2174/1381612825666190215121712.
Cancer is considered a major cause of death worldwide. The etiology of cancer is linked to environmental and genetic inheritance causes. Approximately 90 percent of all human cancers have an environmental cause (non-genetic inheritance) predominantly through lifestyle choices (smoking, diet, UV radiation) while the remaining due to infections and chemical exposure. Cancer is a multistage process that involves mutational changes and uncontrolled cell proliferation. Research has firmly established a causal and contributory role of oxidative stress and oxidative damage in cancer initiation and progression.
The purpose of this article is to review the role that oxidative stress and reactive oxygen species play in the development of cancer. Both endogenous and exogenous sources of reactive oxygen species result in increased oxidative stress in the cell. Excess reactive oxygen fumed can result in damage to and modification of cellular macromolecules most importantly genomic DNA that can produce mutations. In addition, oxidative stress modulates gene expression of downstream targets involved in DNA repair, cell proliferation and antioxidants. The modulation of gene expression by oxidative stress occurs in part through activation or inhibition of transcription factors and second messengers. The role of single nuclear polymorphism for oxidative DNA repair and enzymatic antioxidants is important in determining the potential human cancer risk.
oxidative stress and the resulting oxidative damage are important contributors to the formation and progression of cancer.
癌症被认为是全球主要的死亡原因。癌症的病因与环境和遗传因素有关。大约 90%的人类癌症都有环境原因(非遗传因素),主要是通过生活方式的选择(吸烟、饮食、紫外线辐射),而其余的则是由于感染和化学暴露。癌症是一个多阶段的过程,涉及突变和不受控制的细胞增殖。研究已经明确确立了氧化应激和氧化损伤在癌症发生和发展中的因果和促成作用。
本文的目的是回顾氧化应激和活性氧在癌症发展中的作用。活性氧的内源性和外源性来源都会导致细胞内氧化应激增加。过量的活性氧会导致细胞大分子的损伤和修饰,最重要的是基因组 DNA 的损伤,从而产生突变。此外,氧化应激还可以调节参与 DNA 修复、细胞增殖和抗氧化剂的下游靶基因的表达。氧化应激通过转录因子和第二信使的激活或抑制来调节基因表达。氧化 DNA 修复和酶抗氧化剂的单个核多态性在决定人类癌症风险方面具有重要作用。
氧化应激和由此产生的氧化损伤是癌症形成和发展的重要因素。