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Identification of New Markers of Alcohol-Derived DNA Damage in Humans.

ABSTRACT: Alcohol consumption is a risk factor for the development of several cancers, including those of the head and neck and the esophagus. The underlying mechanisms of alcohol-induced carcinogenesis remain unclear; however, at these sites, alcohol-derived acetaldehyde seems to play a major role. By reacting with DNA, acetaldehyde generates covalent modifications (adducts) that can lead to mutations. Previous studies have shown a dose dependence between levels of a major acetaldehyde-derived DNA adduct and alcohol exposure in oral-cell DNA. The goal of this study was to optimize a mass spectrometry (MS)-based DNA adductomic approach to screen for all acetaldehyde-derived DNA adducts to more comprehensively characterize the genotoxic effects of acetaldehyde in humans. A high-resolution/-accurate-mass data-dependent constant-neutral-loss-MS³ methodology was developed to profile acetaldehyde-DNA adducts in purified DNA. This resulted in the identification of 22 DNA adducts. In addition to the expected N²-ethyldeoxyguanosine (after NaBH₃CN reduction), two previously unreported adducts showed prominent signals in the mass spectra. MSⁿ fragmentation spectra and accurate mass were used to hypothesize the structure of the two new adducts, which were then identified as N⁶-ethyldeoxyadenosine and N⁴-ethyldeoxycytidine by comparison with synthesized standards. These adducts were quantified in DNA isolated from oral cells collected from volunteers exposed to alcohol, revealing a significant increase after the exposure. In addition, 17 of the adducts identified in vitro were detected in these samples confirming our ability to more comprehensively characterize the DNA damage deriving from alcohol exposures.

SUBMITTER: Guidolin V

PROVIDER: S-EPMC7997542 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Alcohol-related brain damage in humans.

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Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

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Identification of GABRA1 and LAMA2 as new DNA methylation markers in colorectal cancer

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2011-12-27 | E-GEOD-26799 | biostudies-arrayexpress

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Identification of a DNA Damage-Induced Alternative Splicing Pathway That Regulates p53 and Cellular Senescence Markers.

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2010-12-15 | E-GEOD-15802 | biostudies-arrayexpress

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