Hirano Takeshi
Department of Life and Environment Engineering, Faculty of Environmental Engineering, The University of Kitakyushu, Kitakyushu, Fukuoka, Japan.
J Radiat Res. 2008 Jul;49(4):329-40. doi: 10.1269/jrr.08049. Epub 2008 Jul 3.
Reactive oxygen species (ROS) are essentially harmful for living organisms, including human beings. It is well known that ROS-induced damage of cellular components may lead to human diseases, such as inflammatory diseases, degenerative diseases, or cancer. In particular, oxidative DNA damage is premutagenic, and thus, the generation of DNA damage and the failure of its removal are critical events for tumorigenesis or carcinogenesis. To prevent this disadvantage, living organisms have defense mechanisms against ROS-induced gene instability. Studies of 8-oxo-Gua and its main repair enzyme, 8-oxoguanine DNA glycosylase 1 (OGG1), are informative and useful, because 8-oxo-Gua is commonly observed in DNA, and OGG1 enzymes exist in a wide variety of living organisms. The importance of OGG1 was confirmed by polymorphism analyses and studies using knockout mice. Moreover, analyses of the influences of environmental factors on DNA damage and repair systems have confirmed the effects of heavy metals on 8-oxo-Gua formation and OGG1 expression. These studies revealed that the 8-oxo-Gua repair system is crucial for the prevention of mutation-related diseases, such as cancer. In this review, the advances in this field during the last two decades are described.
活性氧（ROS）本质上对包括人类在内的生物有害。众所周知，ROS诱导的细胞成分损伤可能导致人类疾病，如炎症性疾病、退行性疾病或癌症。特别是，氧化性DNA损伤具有致突变性，因此，DNA损伤的产生及其修复失败是肿瘤发生或致癌的关键事件。为了避免这种不利情况，生物体具有针对ROS诱导的基因不稳定的防御机制。对8-氧代鸟嘌呤（8-oxo-Gua）及其主要修复酶8-氧代鸟嘌呤DNA糖基化酶1（OGG1）的研究具有重要意义且很有用，因为8-oxo-Gua在DNA中普遍存在，并且OGG1酶存在于多种生物体中。通过多态性分析和使用基因敲除小鼠的研究证实了OGG1的重要性。此外，对环境因素对DNA损伤和修复系统影响的分析证实了重金属对8-oxo-Gua形成和OGG1表达的影响。这些研究表明，8-oxo-Gua修复系统对于预防与突变相关的疾病（如癌症）至关重要。在这篇综述中，描述了该领域在过去二十年中的进展。
