Oxidative DNA Damage and Repair in response to induced ROS exposure in Mice


Meeting Abstract

128-7  Sunday, Jan. 7 11:45 – 12:00  Oxidative DNA Damage and Repair in response to induced ROS exposure in Mice PARK, NP*; ZHANG, Y; HOOD, WR; KAVAZIS, AN; Auburn University nrp0012@auburn.edu

Reactive oxygen species (ROS) can damage mitochondrial and cellular proteins, lipids and DNA and thus, many consider ROS to be consistently harmful. Yet, mitochondria have developed an intricate defense system to mitigate the deleterious effects of ROS and repair damage. Associated with the defense system, mitochondria are hypothesized to display a biphasic response to ROS exposure that is referred to as mitochondrial hormesis, where modest levels of ROS signal increase d mitochondrial biogenesis, antioxidant production, and cell repair of damaged proteins, lipids and DNA. A previous study in our lab characterized the temporal response to induced ROS production in mice via X-irradiation exposure and found that oxidative damage markers for proteins and lipids initially increased and but then dropped to below control levels within 10 days in the liver, heart, skeletal muscle, and brain. The focus of this study is on the damage inflicted upon DNA from ROS. Specifically, we studied temporal changes in oxidative DNA damage and repair associated with ROS exposure via X-irradiation. One of the most stable yet pernicious results markers of oxidative DNA damage is 8-oxo-7,8-dihydroguanine, which results in the transversions of G:C to T:A during replication if not repaired. The primary enzymes involved in repair of this DNA damage are DNA glycosylases, namely 8-oxoguanine glycosylate (OGG1). With this study, we will describe the temporal changes in oxidative DNA damage and repair associated with ROS exposure via X-irradiation. In liver, DNA damage followed the hormetic pattern found in other organs, with the 10-day time-point dropping below the control level (P = 0.022). DNA damage and repair enzyme OGG1 levels in liver, heart, skeletal muscle, and brain will be described.

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