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Arsenic-induced DNA hypomethylation affects chromosomal instability in mammalian cells
Open accessAbstract
Early genetic instability induced in dividing V79-Cl3 Chinese hamster cells by inorganic arsenic, as demonstrated in our previous investigation, was evidenced by aneuploidy and nuclear abnormalities, but not by chromosomal rearrangements. Here we report the results of cytogenetic and morphological analyses performed on the progeny of cells dividing at the end of sodium arsenite treatment after they had been expanded through 120 generations (ASO cells) and then cloned. The acquired genetic instability persisted and was increased by highly unstable chromosomal rearrangements, namely dicentric chromosomes and telomeric associations, which were not seen following acute exposure. A peculiar finding was the preferential involvement of a particular chromosome in dicentric rearrangements observed in some isolated ASO clones. Interestingly, by immunostaining with anti-5-methylcytosine antibodies the genome-wide DNA hypomethylation, induced by arsenic immediately after the acute treatment, was found to affect those ASO clones characterized by aneuploidy and chromosomal rearrangements. These findings demonstrate that short-term exposure to arsenic has long-term effects and suggest that genome-wide DNA hypomethylation enhances genetic instability.
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“Studies have found that arsenic can directly affect DNA repairing efficiency by lowering repair and expression of the nucleotide excision repair pathway member ERCC1 [108, 109].”
From Arsenic Contamination of Groundwater: A Review of Sources, Prevalence, Health Risks, and Strategies for Mitigation (2014) · cites this paper as [108]
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Metadata
- Authors
- Sciandrello, G.
- Affiliations
- University of Palermo (IT)
- Corresponding author
- Sciandrello, G.
- Venue
- Carcinogenesis
- Publisher
- Oxford University Press (OUP)
- Published
- 2003-12-04
- Volume
- 25
- Issue
- 3
- Pages
- 413-417
- ISSN
- 0143-3334 (ISSN-L)
- 1460-2180
- OpenAlex
- W2116476764
- Cited by
- 130
- References
- 25
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 4 · 2022: 6 · 2021: 5 · 2019: 1 · 2018: 1 · 2017: 6 · 2016: 6 · 2015: 9 · 2014: 15 · 2013: 11 · 2012: 10
- FWCI
- 1.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Carcinogenesis (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- inorganic arsenic, sodium arsenite, DNA hypomethylation, chromosomal instability, genomic instability, dicentric chromosomes, chromosomal rearrangements, aneuploidy, telomeric associations, 5-methylcytosine, long-term exposure effects
- MeSH terms
- Animals, Antineoplastic Agents, Arsenic, Carcinogens, Chromosome Aberrations, Cricetinae, DNA Methylation, Cytogenetic Analysis, Chromosomal Instability
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