Excess processing of oxidative damaged bases causes hypersensitivity to oxidative stress and low dose rate irradiation. (October 2015)

• Record Type: Journal Article
• Authors: Yoshikawa, Y.; Yamasaki, A.; Takatori, K.; Suzuki, M.; Kobayashi, J.; Takao, M.; Zhang-Akiyama, Q.-M.
• Is Part Of: Free radical research. Volume 49:Number 10(2015:Oct.)
• Page Start: 1239
• Page End: 1248
• Publication Date: 2015-10
• Subjects: Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• Languages: English
• ISSNs: 1071-5762

Abstract

<abstract> <title>Abstract</title> <p>Ionizing radiations such as X-ray and γ-ray can directly or indirectly produce clustered or multiple damages in DNA. Previous studies have reported that overexpression of DNA glycosylases in <italic>Escherichia coli</italic> (<italic>E. coli</italic>) and human lymphoblast cells caused increased sensitivity to γ-ray and X-ray irradiation. However, the effects and the mechanisms of other radiation, such as low dose rate radiation, heavy-ion beams, or hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), are still poorly understood. In the present study, we constructed a stable HeLaS3 cell line overexpressing human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) protein. We determined the survival of HeLaS3 and HeLaS3/hOGG1 cells exposed to UV, heavy-ion beams, γ-rays, and H<sub>2</sub>O<sub>2</sub>. The results showed that HeLaS3 cells overexpressing hOGG1 were more sensitive to γ-rays, OH<sup></sup>, and H<sub>2</sub>O<sub>2</sub>, but not to UV or heavy-ion beams, than control HeLaS3. We further determined the levels of 8-oxoG foci and of chromosomal double-strand breaks (DSBs) by detecting γ-H2AX foci formation in DNA. The results demonstrated that both γ-rays and H<sub>2</sub>O<sub>2</sub> induced 8-oxoguanine (8-oxoG) foci formation in HeLaS3 cells. hOGG1-overexpressing cells had increased amounts of γ-H2AX foci and decreased amounts of 8-oxoG foci compared with HeLaS3 control cells. These results suggest that excess hOGG1 removes the oxidatively damaged 8-oxoG in DNA more efficiently and therefore generates more DSBs. Micronucleus formation also supported this conclusion. Low dose-rate γ-ray effects were also investigated. We first found that overexpression of hOGG1 also caused increased sensitivity to low dose rate γ-ray irradiation. The rate of micronucleus formation supported the notion that low dose rate irradiation increased genome instability.</p> </abstract>