ArticleCarcinogenesis2020
Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice.
Article in Carcinogenesis, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Association Study and Meta-Analysis of Polymorphisms and Blood mRNA Expression of the ALDH2 Gene in Patients with Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2022Pooled it
- Ethnic genomic diversity in esophageal squamous cell carcinoma.World journal of gastrointestinal oncology · 2026Review
- Integrative Mendelian Randomization and Single-Cell Pseudotime Analysis Reveal DKK3 as a PI3K-AKT-Modulated Driver of Esophageal Squamous Cell Carcinoma.Human mutation · 2026Article
- Alda‑1 restores ALDH2‑mediated alcohol metabolism to inhibit the NF‑κB/VEGFC axis in head and neck cancer.International journal of molecular medicine · 2025Article
- [Research progress of aldehyde dehydrogenase type 2 in head and neck malignant tumors].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Dietary Polyphenols: Review on Chemistry/Sources, Bioavailability/Metabolism, Antioxidant Effects, and Their Role in Disease Management.Antioxidants (Basel, Switzerland) · 2024Review
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells.iScience · 2023Article
- Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons.Aging cell · 2023Article
- Can gene therapy be used to prevent cancer? Gene therapy for aldehyde dehydrogenase 2 deficiency.Cancer gene therapy · 2022Review
- Activation of aldehyde dehydrogenase 2 protects ethanol-induced osteonecrosis of the femoral head in rat model.Cell proliferation · 2022Article
- A commentary on the paper: 'Evaluation of spice and herb as phytoderived selective modulators of human retinaldehyde dehydrogenases using a simple in vitro method'.Bioscience reports · 2022Article
- FANCD2 limits acetaldehyde-induced genomic instability during DNA replication in esophageal keratinocytes.Molecular oncology · 2021Article
- Systemic Adeno-Associated Virus-Mediated Gene Therapy Prevents the Multiorgan Disorders Associated with Aldehyde Dehydrogenase 2 Deficiency and Chronic Ethanol Ingestion.Human gene therapy · 2020Article
- Treatment outcomes for one-stage concurrent surgical resection and reconstruction of synchronous esophageal and head and neck squamous cell carcinoma.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2019Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alcohol consumption is the key risk factor for the development of esophageal squamous cell carcinoma (ESCC), and acetaldehyde, a metabolite of alcohol, is an alcohol-derived major carcinogen that causes DNA damage. Aldehyde dehydrogenase2 (ALDH2) is an enzyme that detoxifies acetaldehyde, and its activity is reduced by ALDH2 gene polymorphism. Reduction in ALDH2 activity increases blood, salivary and breath acetaldehyde levels after alcohol intake, and it is deeply associated with the development of ESCC. Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC; however, effective prevention has not been established yet. In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2 and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-2'-deoxyguanosine). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice and reduced esophageal DNA damage levels after alcohol drinking. Conversely, cyanamide, an ALDH2-inhibitor, significantly exacerbated esophageal DNA adduct level in C57BL/6N mice induced by alcohol drinking. These results indicate the protective effects of ALDH2 activation by Alda-1 on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism, providing a new insight into acetaldehyde-mediated esophageal carcinogenesis and prevention.
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Registered trials
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