文章：

DNA甲基化标记的力量和前景

Radical causes of cancer

原文发布日期：2003-04-01

DOI: 10.1038/nrc1046

类型: Review Article

开放获取: 否

要点：

1. Chronic inflammation deregulates cellular homeostasis and can drive carcinogenesis.
2. Free radicals and aldehydes — produced during chronic inflammation — can induce a number of alterations, including gene mutations and post-translational modifications of key cancer-related proteins. These alterations can lead to the disruption of cellular processes such as DNA repair, cell-cycle checkpoints and apoptosis.
3. The ultimate effect of free radicals is complex and depends on their local concentration, the microenvironment and the genetic background of the individual.
4. Nitric oxide and its derivatives damage DNA and modify protein structure and function but can also protect from cytotoxicity. These 'two faces' of nitric oxide highlight the need for further study before considering nitric oxide as a target for chemoprevention in high cancer risk, chronic inflammatory diseases.
5. People with cancer-prone inflammatory diseases, such as ulcerative colitis, haemochromatosis and viral hepatitis, have alterations in cancer-related genes and proteins,which are associated with free-radical stress.
6. Transgenic and knockout animal models support the role of free radicals in carcinogenesis.
7. Prospective chemoprevention studies are needed to evaluate the use of antioxidants and inhibitors of pro-oxidant enzymes for the prevention of cancer in people with oxyradical overload diseases.

要点翻译：

1. 慢性炎症会扰乱细胞稳态并可能驱动癌变。
2. 慢性炎症过程中产生的自由基和醛类物质可诱发多种改变，包括基因突变和关键癌症相关蛋白的翻译后修饰。这些改变可能导致DNA修复、细胞周期检查点和凋亡等细胞过程失调。
3. 自由基的最终效应十分复杂，取决于其局部浓度、微环境及个体遗传背景。
4. 一氧化氮及其衍生物会损伤DNA并改变蛋白质结构与功能，但同时也具有细胞毒性保护作用。一氧化氮的这种"双面性"表明，在考虑将其作为高癌症风险慢性炎症性疾病化学预防靶点之前，仍需进一步研究。
5. 患有易癌变炎症性疾病（如溃疡性结肠炎、血色素沉着症和病毒性肝炎）的人群，其癌症相关基因和蛋白质存在改变，这些改变与自由基应激相关。
6. 转基因和基因敲除动物模型支持自由基在癌变中的作用。
7. 需要进行前瞻性化学预防研究，以评估使用抗氧化剂和促氧化酶抑制剂预防氧自由基过载疾病患者癌症的效果。

英文摘要：

Free radicals are ubiquitous in our body and are generated by normal physiological processes, including aerobic metabolism and inflammatory responses, to eliminate invading pathogenic microorganisms. Because free radicals can also inflict cellular damage, several defences have evolved both to protect our cells from radicals — such as antioxidant scavengers and enzymes — and to repair DNA damage. Understanding the association between chronic inflammation and cancer provides insights into the molecular mechanisms involved. In particular, we highlight the interaction between nitric oxide and p53 as a crucial pathway in inflammatory-mediated carcinogenesis.

摘要翻译： 

自由基在体内无处不在，由正常生理过程产生，包括有氧代谢和旨在清除入侵病原微生物的炎症反应。由于自由基也能造成细胞损伤，机体已进化出多种防御机制：既有抗氧化清除剂和酶等保护细胞免受自由基侵害的系统，也有修复DNA损伤的机制。理解慢性炎症与癌症之间的关联，可揭示其分子机制。我们特别强调一氧化氮与p53的相互作用是炎症介导致癌过程中的关键通路。

原文链接：

Radical causes of cancer