Oxidative damage to DNA and single strand break repair capacity: Relationship to other measures of oxidative stress in a population cohort

Abstract

It is well accepted that oxidative DNA repair capacity, oxidative damage to DNA and oxidative stress play central roles in aging and disease development. However, the correlation between oxidative damage to DNA, markers of oxidant stress and DNA repair capacity is unclear. In addition, there is no universally accepted panel of markers to assess oxidative stress in humans. Our interest is oxidative damage to DNA and its correlation with DNA repair capacity and other markers of oxidative stress. We present preliminary data from a small comet study that attempts to correlate single strand break (SSB) level with single strand break repair capacity (SSB-RC) and markers of oxidant stress and inflammation. In this limited study of four very small age-matched 24-individual groups of male and female whites and African-Americans aged 30–64 years, we found that females have higher single strand break (SSB) levels than males (p=0.013). There was a significant negative correlation between SSB-RC and SSB level (p=0.041). There was a positive correlation between SSBs in African American males with both heme degradation products (p=0.008) and high-sensitivity C-reactive protein (hs-CRP) (p=0.022). We found a significant interaction between hs-CRP and sex in their effect on residual DNA damage (p=0.002). Red blood cell reduced glutathione concentration was positively correlated with the levels of oxidized bases detected by endonuclease III (p=0.047), heme degradation products (p=0.015) and hs-CRP (p=0.020). However, plasma carbonyl levels showed no significant correlation with other markers. The data from the literature and from our very limited study suggest a complex relationship between measures of oxidative stress and frequently used clinical parameters believed to reflect inflammation or oxidative stress.

Age and gender effects on DNA strand break repair in peripheral blood mononuclear cells

“…Previous studies investigating SSBR in peripheral blood mononuclear cells (PBMCs) from donors of different age suggested minor or no effect on age (Muller et al , 2001; Zana et al , 2006; Trzeciak et al , 2008, 2012). Some reports have suggested an age-related increase of endogenous SSBs in human PBMCs (Mutlu-Turkoglu et al , 2003; Moller, 2006; Humphreys et al , 2007), whereas others have suggested no age effect (Slyskova et al , 2011).…”

Biomarkers of Oxidative Stress in Blood

“…Noncoding RNA species, such as transfer RNAs, microRNAs, and small nuclear and nucleolar RNAs, are also susceptible to oxidation (Kong et al 2008;Jacob et al 2013). The known molecular consequences of RNA oxidation are premature termination of reverse transcription, ribosomal dysfunction, aberrant and reduced protein synthesis, and translation of truncated or mutated proteins that are nonfunctional or prone to misfolding or aggregation (Rhee et al 1995;van Leeuwen et al 1998;Tanaka et al 2007;).…”

“…Carbonyls measured in tissues tend to have significant variation (Dalle-Donne et al 2003;Jacob et al 2013). Furthermore, studies have generally failed to find significant and strong correlation of plasma carbonyls to presence of nucleic acid lesions (Trzeciak et al 2012).…”

“…Fluorescent heme degradation products correlate to PBMC and SSB indicators of oxidative stress and DNA damage. This correlation makes this marker ideal for clinical use, as measurements represent systemic oxidative stress while remaining simple, rapid, and less subject to variation than some other methods (Trzeciak et al 2012). …”

“…Erythrocyte GSH also correlates with other markers of oxidative stress, and there is a positive correlation with SSBs and SSB repair capacity. There is a strong correlation between erythrocyte GSH levels and the presence of heme degradation products (Trzeciak et al 2012;Jacob et al 2013). Few studies of aging have however been contradictory, finding no difference in GSH levels with aging (Kasapoglu and Ozben 2001;Kedziora-Kornatowska et al 2007).…”