ArticleGenes and environment : the official journal of the Japanese Environmental Mutagen Society2020
The failure of two major formaldehyde catabolism enzymes (ADH5 and ALDH2) leads to partial synthetic lethality in C57BL/6 mice.
Article in Genes and environment : the official journal of the Japanese Environmental Mutagen Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 44 citations in OpenAlex.
- Aldehyde Detoxification in Cancer: Metabolic Guardians of the Genome.Biomolecules · 2026Review
- Metabolic trajectories in developing human neocortical neurons.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Formate Reduces Ischemic Injury in Female Hearts Lacking Alcohol Dehydrogenase 5.FASEB bioAdvances · 2025Article
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- Effect of HScientific reports · 2025Article
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- Emerging bone marrow failure syndromes- new pieces to an unsolved puzzle.Frontiers in oncology · 2023Review
- Acute high-altitude hypoxia exposure causes neurological deficits via formaldehyde accumulation.CNS neuroscience & therapeutics · 2022Article
- Aldh2 is a lineage-specific metabolic gatekeeper in melanocyte stem cells.Development (Cambridge, England) · 2022Article
- Comparative transcriptome and metabolome analyses reveal the methanol dissimilation pathway of Pichia pastoris.BMC genomics · 2022Article
- Perspectives on formaldehyde dysregulation: Mitochondrial DNA damage and repair in mammalian cells.DNA repair · 2021Review
- Accumulation of formaldehyde causes motor deficits in an in vivo model of hindlimb unloading.Communications biology · 2021Article
- Genomics as a Clinical Decision Support Tool: Successful Proof of Concept for Improved ASD Outcomes.Journal of personalized medicine · 2021Article
- ALDH2 polymorphism rs671 is a predictor of PD-1/PD-L1 inhibitor efficacy against thoracic malignancies.BMC cancer · 2021Observational
- Formation and repair of unavoidable, endogenous interstrand cross-links in cellular DNA.DNA repair · 2021Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundExogenous formaldehyde is classified by the IARC as a Category 1 known human carcinogen. Meanwhile, a significant amount of endogenous formaldehyde is produced in the human body; as such, formaldehyde-derived DNA and protein adducts have been detected in animals and humans in the absence of major exogenous formaldehyde exposure. However, the toxicological effects of endogenous formaldehyde on individuals with normal DNA damage repair functions are not well understood. In this study, we attempted to generate C57BL/6 mice deficient in both
resultsDue to deficiencies in both ADH5 and ALDH2, few mice survived past post-natal day 21. In fact, the survival of pups within the first few days after birth was significantly decreased. Remarkably, two
conclusionMice deficient in both formaldehyde-metabolizing enzymes ADH5 and ALDH2 were found to develop partial synthetic lethality and mortality shortly after birth. This phenotype may be due to the accumulation of endogenous formaldehyde. No serious phenotype has been reported in people with dysfunctional, dominant-negative
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