Abstract
Abstract Reactive oxygen species (ROS) produced from cellular metabolism and exposure to environmental agents pose a significant threat to genomic stability. Direct DNA oxidation by ROS or indirect modification by products of lipid peroxidation results in the formation of mutagenic DNA adducts that are implicated in carcinogenesis. Following oxidation of phospholipid and/or DNA, several reactive aldehydes are formed including base propenal and malondialdehyde (MDA), both of which can react with DNA to form oxopropenyl-adducted bases. The most abundant DNA adduct produced, M1dG, is the product of reaction with deoxyguanosine. This adduct has been extensively characterized and shown to be mutagenic in both mammalian and bacterial systems and repaired by the nucleotide excision repair (NER) pathway. M1dG has also been detected in the genomic DNA of both healthy and disease-bearing individuals, indicating its presence and significance in cellular metabolism. Previous work has demonstrated that M1dG is oxidized in rats to a single metabolite, 6-oxo-M1dG, which can be detected in both urine and feces and has the potential to be used as a biomarker for oxidative stress and disease. We have developed antibodies against M1dG and 6-oxo-M1dG, which are being utilized in a novel assay for the analysis of M1dG and 6-oxo-M1dG in biological samples. Using solid phase extraction and mass spectrometry, we have developed a reliable assay for the analysis of 6-oxo-M1dG in urine and feces from male Sprague-Dawley rats. We have determined the level of excreted 6-oxo-M1dG to be 0.19 pmol/kg/day in urine and 0.92 pmol/kg/day in feces. We are currently expanding our studies to analyze samples from animals with increased oxidative stress in order to determine how excretion and metabolism of M1dG is altered under these conditions. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5733. doi:1538-7445.AM2012-5733
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