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

Details

• Personal Author:
  Balbo S ; Carlson ES ; Carrà A ; Guidolin V ; Hecht SS ; Maertens LA ; Villalta PW
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Alcoholic Beverages Biomarkers Carcinogens Mutagens Neoplasms Occupational Health Safety
• Keywords:
  Acetaldehyde Acetaldehydes Adductomics Adenosines Alcohol Alcoholic Beverages Alcohols Author Keywords: Acetaldehyde Cancer Cell Alteration Cell Differentiation Cellular Effects DNA Adducts DNA Damage Genotoxic Effects Humans Mass Spectrometry Mutagenicity Oral Toxicity

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• ISSN:
  2218-273X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Minnesota ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  11
• Issue:
  3
• NIOSHTIC Number:
  nn:20062198
• Citation:
  Biomolecules 2021 Mar; 11(3):366
• Contact Point Address:
  Silvia Balbo, Division of Environmental Health Sciences, University of Minnesota, Minneapolis, MN 55455, USA
• Email:
  balbo006@umn.edu
• CAS Registry Number:
  Acetaldehyde (CAS RN 75-07-0) ; N(6)-Methyladenosine (CAS RN 1867-73-8)
• Federal Fiscal Year:
  2021
• Performing Organization:
  University of Minnesota Twin Cities
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  Biomolecules
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:98ea8e7d3eb6325ecee35a26802e3937ec52cca17b1d4e18166d698b7c3a5129f5228e14406b34e57ffce11bbd68590f9dc817caecf86d130d77cd1e5bea4c81
• Download URL:
  https://stacks.cdc.gov/view/cdc/225494/cdc_225494_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]