Nitric oxide and oxygen radicals in infection, inflammation, and cancer.
Nitric oxide and oxygen radicals in infection, inflammation, and cancer.
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发表时间：
1998-07
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通讯作者：
H. Maeda;T. Akaike
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作者：
H. Maeda;T. Akaike
近年来，越来越多的证据表明，自由基和一氧化氮（NO）及其衍生物是致癌的关键因素。我们目前在这篇文章中讨论的主题将集中在由病毒和细菌感染诱导的自由基产生的生物学意义。流感病毒感染小鼠后，感染部位黄嘌呤氧化酶（XO）水平明显升高。XO与诱导型NO合酶（iNOS）的相互作用时间表明NO + O2*-> ONOO-（过氧亚硝酸根）是有效的同步反应。过氧亚硝酸盐的形成，确定了免疫染色的硝基酪氨酸在当地网站的感染器官。过氧亚硝酸盐具有独特的化学反应性，如蛋白质硝化、DNA链断裂、鸟嘌呤硝化等，这不仅可能导致细胞毒性作用，而且可能导致诱变。大量的体外和体内实验证据表明，用化学致癌物如四氯化碳和杂环胺处理也会产生超氧化物。慢性炎症反应，例如，酵母多糖和二氧化硅诱导的肉芽肿，揭示了非常相似的体内自由基生成。此外，大多数实验性实体瘤在肿瘤组织中具有升高的iNOS水平，并且由此产生的NO促进血管通透性，这加速了对肿瘤组织的营养供应，从而维持了肿瘤的快速生长。这些间接证据表明，由各种病原体诱导的炎症反应将加速诱变以及组织损伤，而NO也更有效地维持实体瘤生长时，正常细胞转化为肿瘤或癌细胞的宿主衍生的自由基物种。
In recent years, accumulated evidence indicates that free radical species and nitric oxide (NO) or its derivatives are the key denominators in carcinogenesis. Our present topics discussed in this article will focus on the biological significance of free radical generation induced by viral and bacterial infections. In influenza virus infection in mice, the level of xanthine oxidase (XO) at the infected sites was elevated to a great extent. The timing of paralleled induction of XO with that of inducible NO synthase (iNOS) indicates efficient simultaneous reaction: NO + O2*- --> ONOO- (peroxynitrite). Peroxynitrite formation was identified by immunostaining of nitrotyrosine at the local site of infected organs. Peroxynitrite exhibits unique chemical reactivities such as protein nitration, DNA-strand breakage, guanine nitration, etc., which may then bring about not only cytotoxic effect but also mutagenesis. Numbers of evidence in vitro and in vivo show that treatment with chemical carcinogens such as carbon tetrachloride and heterocyclic amines also generated superoxide. The chronic inflammatory reactions, e.g., zymosan- and silica-induced granuloma, revealed very similar free radical generation in vivo. In addition, most experimental solid tumors have elevated levels of iNOS in the tumor tissue, and NO thus generated facilitates vascular permeability, which accelerates nutritional supply to the tumor tissue and hence sustains the rapid tumor growth. These circumstantial evidences suggest that inflammatory responses induced by various pathogens would accelerate mutagenesis as well as tissue damage, whereas NO also sustains more effectively solid tumor growth when normal cells are transformed to tumor or carcinoma cells by the host-derived free radical species.