There is extensive evidence in the literature linking chronic inflammation and carcinogenesis. Chronic inflammation can produce reactive oxygen species (ROS) that oxidize cellular molecules including lipids and DNA. Our laboratory has shown that 3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG) is the most abundant DNA adduct formed from the lipid peroxidation product, malondialdehyde, or the DNA peroxidation product, base propenal. M1dG is mutagenic in bacterial and mammalian cells and is repaired by the nucleotide excision repair system. We report that M1dG is present at significant levels in a variety of human and murine cell types and that it is oxidized in intact DNA to a single oxidation product, 6-oxo-M1dG. This is the first report of the production of 6-oxo-M1dG in genomic DNA and it has significant implications for understanding the role of inflammation in DNA damage, mutagenesis and repair. 6-Oxo-M1dG appears to be one of the most abundant adducts in genomic DNA yet little is known of its formation or mutagenic potential.

Nuclear metabolism of an inflammation-linked DNA adduct in the genome

250th National Meeting (2015)

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