Repair system of 7, 8-dihydro-8-oxoguanine as a defense line against carcinogenesis

• Published in: Journal of radiation research 2008-07, Vol.49 (4), p.329-340
• Main Author: Hirano, Takeshi
• Format: Article
• Language: English
• Subjects: Animals; Cancer; Carcinogenesis; Defense mechanisms; DNA Damage; DNA glycosylase; DNA Glycosylases - metabolism; DNA Repair; Environmental factors; Enzymes; Guanine - analogs & derivatives; Guanine - metabolism; Heavy metals; Humans; Inflammatory diseases; Neoplasms, Radiation-Induced - metabolism; Neoplasms, Radiation-Induced - prevention & control; OGG1 protein; Radiation Tolerance; Reactive oxygen species; Reactive Oxygen Species - metabolism; Tumorigenesis
• ISSN: 0449-3060; 1349-9157; 1349-9157
• DOI: 10.1269/jrr.08049

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.