Oxidative DNA Damage: Mechanisms and Significance in Health and Disease

摘要

REACTIVE OXYGEN SPECIES (ROS) are implicated as a cause of cancer and lifestyle-related diseases. Ionizing radiation and many environmental chemicals generate ROS and damage DNA. ROS are also produced endogenously as a by-product of oxygen metabolism. Therefore, ROS may also be involved in the aging process. 8-Hydroxydeoxyguanosine (8-OH-dG, 7,8-dihydro-8-oxodeoxyguanosine) was discovered in 1983 during an in vitro study of DNA modifications caused by mutagens produced by heating carbohydrates, which were being used as a model of cooked foods (9-11). In 1986, Floyd et al. developed a sensitive method to analyze 8-OH-dG using an electrochemical detector with high performance liquid chromatography (HPLC-ECD) (4). This method revealed that various ROS-forming carcinogens induce an increase of 8-OH-dG in cellular DNA (12, 13). Ames and his collaborators were the first to detect 8-OH-dG in animal and human urine samples by HPLC-ECD (24, 26). These discoveries triggered further studies on mutagenesis, oxidative DNA damage repair enzymes, and the molecular epidemiology of various ROS-related diseases. Patients with cancer (urine), chronic hepatitis (urine), diabetes (urine, leukocyte DNA), heart disease (leukocyte DNA), Alzheimer's disease (urine), Parkinson's disease (urine), atopic dermatitis (urine), as well as premature babies (urine), showed higher levels of 8-OH-dG (3, 7, 16, 18, 19, 21, 25, 28, 30, 31). In contrast, the consumption of vitamins E and C, lutein, p-cryptoxanthin, vegetables, fruit, green tea, and tomato sauce was correlated with a reduction in the amount of 8-OH-dG in urine or leukocyte DNA (1, 5, 6, 8, 15, 29). Therefore, 8-OH-dG is a useful marker for monitoring cellular oxidative stress involved in the induction of cancer and lifestyle-related diseases and their prevention by antioxidants. During the last 2 decades, publications on 8-OH-dG have increased as shown in Fig. 1. In parallel, publications on urinary 8-OH-dG (Fig. 2) and the inhibition of 8-OH-dG by antioxidants (Fig. 3) also increased