Timeless insights into prevention of acetaldehyde genotoxicity?

Brooks, Philip J.; Schuebel, Kornel E.

doi:10.1080/15384101.2016.1247570

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Alcohol consumption. Acetaldehyde, the first metabolite in alcohol degradation, induces crosslinks and forms adducts with DNA and proteins [126,127]. There are several human studies in which the effect of alcohol consumption on the DNA damage has been studied using the comet assay.…”

Section: Physical Activitymentioning

confidence: 99%

Application of the comet assay in human biomonitoring: An hCOMET perspective

Azqueta

Ladeira

Giovannelli

et al. 2020

Mutation Research/Reviews in Mutation Research

114

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The comet assay is a well-accepted biomonitoring tool to examine the effect of dietary, lifestyle, environmental and occupational exposure on levels of DNA damage in human cells. With such a wide range of determinants for DNA damage levels, it becomes challenging to deal with confounding and certain factors are interrelated (e.g. poor nutritional intake may correlate with smoking status). This review describes the effect of intrinsic (i.e. sex, age, tobacco smoking, occupational exposure and obesity) and extrinsic (season, environmental exposures, diet, physical activity and alcohol consumption) factors on the level of DNA damage measured by the standard or enzyme-modified comet assay. Although each factor influences at least one comet assay endpoint, the collective evidence does not indicate single factors have a large impact. Thus, controlling for confounding may be necessary in a biomonitoring study, but none of the factors is strong enough to be regarded a priori as a confounder. Controlling for confounding in the comet assay requires a case-by-case approach. Inter-laboratory variation in levels of DNA damage and to some extent also reproducibility in biomonitoring studies are issues that have haunted the users of the comet assay for years. Procedures to collect specimens, and their storage, are not standardized. Likewise, statistical issues related to both sample-size calculation (before sampling of specimens) and statistical analysis of the results vary between studies. This review gives guidance to statistical analysis of the typically complex exposure, co-variate, and effect relationships in human biomonitoring studies.

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Section: Physical Activitymentioning

confidence: 99%

Application of the comet assay in human biomonitoring: An hCOMET perspective

Azqueta

Ladeira

Giovannelli

et al. 2020

Mutation Research/Reviews in Mutation Research

114

View full text Add to dashboard Cite

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“…The nucleotide excision repair (NER) pathway repairs PdG adducts (Johnson et al, 1997) and thus likely mitigates acetaldehyde-induced DNA damage. A comprehensive functional screen in fission yeast demonstrated key roles for the FA, HR, and NER pathways in modulating acetaldehyde toxicity and reveled roles for base excision repair (BER), translesion DNA synthesis (TLS) and DNA-protein crosslink (DPC) repair in reversing acetaldehyde-induced DNA damage (Brooks and Schuebel, 2017;Noguchi et al, 2017). To our knowledge, a similar large-scale genomic approach to study mechanisms affecting cellular sensitivity and tolerance to acetaldehyde in mammalian, and particularly human cells, has not been performed.…”

mentioning

confidence: 99%

Genome-Wide CRISPR Screening Identifies the Tumor Suppressor Candidate OVCA2 As a Determinant of Tolerance to Acetaldehyde

Sobh

Loguinov

Stornetta

et al. 2019

Toxicological Sciences

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Acetaldehyde, a metabolite of ethanol, is a cellular toxicant and a human carcinogen. A genome-wide CRISPR-based loss-of-function screen in erythroleukemic K562 cells revealed candidate genetic contributors affecting acetaldehyde cytotoxicity. Secondary screening exposing cells to a lower acetaldehyde dose simultaneously validated multiple candidate genes whose loss results in increased sensitivity to acetaldehyde. Disruption of genes encoding components of various DNA repair pathways increased cellular sensitivity to acetaldehyde. Unexpectedly, the tumor suppressor gene OVCA2, whose function is unknown, was identified in our screen as a determinant of acetaldehyde tolerance. Disruption of the OVCA2 gene resulted in increased acetaldehyde sensitivity and higher accumulation of the acetaldehyde-derived DNA adduct N2-ethylidene-dG. Together these results are consistent with a role for OVCA2 in adduct removal and/or DNA repair.

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