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首页> 外文期刊>AIMS Genetics >DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity
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DNA damage by lipid peroxidation products: implications in cancer, inflammation and autoimmunity

机译：脂质过氧化产物对DNA的损害：对癌症，炎症和自身免疫的影响

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Oxidative stress and lipid peroxidation (LPO) induced by inflammation, excess metal storage and excess caloric intake cause generalized DNA damage, producing genotoxic and mutagenic effects. The consequent deregulation of cell homeostasis is implicated in the pathogenesis of a number of malignancies and degenerative diseases. Reactive aldehydes produced by LPO, such as malondialdehyde, acrolein, crotonaldehyde and 4-hydroxy-2-nonenal, react with DNA bases, generating promutagenic exocyclic DNA adducts, which likely contribute to the mutagenic and carcinogenic effects associated with oxidative stress-induced LPO. However, reactive aldehydes, when added to tumor cells, can exert an anticancerous effect. They act, analogously to other chemotherapeutic drugs, by forming DNA adducts and, in this way, they drive the tumor cells toward apoptosis. The aldehyde-DNA adducts , which can be observed during inflammation, play an important role by inducing epigenetic changes which, in turn, can modulate the inflammatory process. The pathogenic role of the adducts formed by the products of LPO with biological macromolecules in the breaking of immunological tolerance to self antigens and in the development of autoimmunity has been supported by a wealth of evidence. The instrumental role of the adducts of reactive LPO products with self protein antigens in the sensitization of autoreactive cells to the respective unmodified proteins and in the intermolecular spreading of the autoimmune responses to aldehyde-modified and native DNA is well documented. In contrast, further investigation is required in order to establish whether the formation of adducts of LPO products with DNA might incite substantial immune responsivity and might be instrumental for the spreading of the immunological responses from aldehyde-modified DNA to native DNA and similarly modified, unmodified and/or structurally analogous self protein antigens, thus leading to autoimmunity.
机译：炎症，过多的金属存储和过多的热量摄入引起的氧化应激和脂质过氧化（LPO）会引起普遍的DNA损伤，产生遗传毒性和诱变作用。细胞稳态的随之而来的失调与许多恶性肿瘤和变性疾病的发病机理有关。 LPO产生的反应性醛，例如丙二醛，丙烯醛，巴豆醛和4-羟基-2-壬烯醛，与DNA碱基发生反应，生成促突变的环外DNA加合物，这可能与氧化应激诱导的LPO相关的致突变和致癌作用有关。但是，将活性醛添加到肿瘤细胞后，可以发挥抗癌作用。它们与其他化疗药物相似，通过形成DNA加合物起作用，并以此方式驱动肿瘤细胞凋亡。醛-DNA加合物（在炎症过程中可以观察到）通过诱导表观遗传变化而发挥重要作用，而表观遗传变化又可以调节炎症过程。 LPO产物与生物大分子形成的加合物在破坏对自身抗原的免疫耐受性和自身免疫发展中的致病作用已得到大量证据的支持。充分证明了反应性LPO产物与自身蛋白抗原的加合物在自身反应性细胞对各自未修饰的蛋白质致敏以及对醛修饰的天然DNA的自身免疫应答的分子间扩散中的作用。相反，需要进一步研究以确定LPO产物与DNA的加合物的形成是否会引起实质性的免疫反应，并且可能有助于从醛修饰的DNA到天然DNA以及相似修饰的，未修饰的免疫反应的传播和/或结构类似的自身蛋白抗原，从而导致自身免疫。

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