Molecular mechanisms of oxidative stress‐induced carcinogenesis: From epidemiology to oxygenomics
Molecular mechanisms of oxidative stress‐induced carcinogenesis: From epidemiology to oxygenomics
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DOI：
10.1002/iub.61
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发表时间：
2008-07
期刊：
影响因子：
4.6
通讯作者：
S. Toyokuni
中科院分区：
文献类型：
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作者：
S. Toyokuni
氧化应激与炎症、辐射、再灌注和铁超载有关。流行病学观察表明，氧化应激是致癌的主要来源之一，是全球人类死亡的首要原因。在氧化应激的情况下，活性氧和氮物质有助于基因组信息的改变，推测随后是在给定环境中选择适应的增殖细胞。最近的数据表明，常见的分子机制存在于氧化应激诱导的致癌作用中，包括p16 INK 4A失活。到目前为止，作为突变原因的基因组中的氧化性DNA损伤已经被认为是基于体外实验随机分布的，而体内氧化性DNA损伤的定位还没有被追求。然而，使用基于DNA免疫沉淀结合基因组信息的新技术，我们现在知道氧化DNA损伤的定位在体内不是随机的。我们建议将这一相当新颖的研究领域称为“氧组学”。许多信号通路从识别DNA损伤开始。因此，可能的基本原则，应阐明与每种细胞类型，基因组位置的损害，其转录活性以及染色质状态决定的表观遗传效应。© 2008 IUBMB IUBMB Life，60（7）：441-447，2008
Oxidative stress is associated with inflammation, radiation, reperfusion, and iron overload. Epidemiological observations have shown that oxidative stress is one of the major sources of carcinogenesis, the top‐ranked cause of human mortality worldwide. In situations of oxidative stress, reactive oxygen and nitrogen species contribute to the alteration of genome information, presumably followed by selection of the adapted proliferating cells in a given environment. Recent data suggest that common molecular mechanisms exist in oxidative stress‐induced carcinogenesis, including p16INK4A inactivation. Thus far, oxidative DNA damage in the genome as a cause of mutation has been recognized to be randomly distributed based on in vitro experiments, while localization of oxidative DNA damage in vivo has not been pursued. However, using a novel technique based on DNA immunoprecipitation in combination with genome information, we now know that the localization of oxidative DNA damage is not random in vivo. We propose to call this rather novel research area “oxygenomics.” Many signaling pathways start from the recognition of DNA damage. Thus, possible underlying principles should be elucidated in association with each cell type, the genomic location of the damage with its transcriptional activity as well as the chromatin status determining the epigenetic effect. © 2008 IUBMB IUBMB Life, 60(7): 441–447, 2008