Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

Fujioka, Masaki; Gi, Min; Kawachi, Satoko; Tatsumi, Kumiko; Ishii, Naomi; Doi, Kenichiro; Kakehashi, Anna; Wanibuchi, Hideki

doi:10.1016/j.jes.2016.07.005

Cited by 6 publications

(2 citation statements)

References 35 publications

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“…DMA V is non-mutagenic in in vitro tests [1,21]. Our previous study demonstrated that DMA V is not mutagenic in the bladders of gpt delta rats [22]. We also found that transplacental DMA V exposure leads to aberrant methylation of histone H3K9, subsequent overexpression of Krt8, and increased cellular proliferation, thereby enhancing lung carcinogenesis in male offspring mice [23].…”

Section: Introductionmentioning

confidence: 94%

DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis

Yamamoto,

Gi,

Yamashita

et al. 2023

Cancers

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Arsenic is a known human urinary bladder carcinogen. While arsenic is known to cause aberrant DNA methylation, the mechanism of arsenic-triggered bladder carcinogenesis is not fully understood. The goal of this study was to identify aberrant DNA methylation in rat bladder urothelial carcinoma (UC) induced by dimethylarsinic acid (DMAV), a major organic metabolite of arsenic. We performed genome-wide DNA methylation and microarray gene expression analyses of DMAV-induced rat UCs and the urothelium of rats treated for 4 weeks with DMAV. We identified 40 genes that were both hypermethylated and downregulated in DMAV-induced rat UCs. Notably, four genes (CPXM1, OPCML, TBX20, and KCND3) also showed reduced expression in the bladder urothelium after 4 weeks of exposure to DMAV. We also found that CPXM1 is aberrantly methylated and downregulated in human bladder cancers and human bladder cancer cells. Genes with aberrant DNA methylation and downregulated expression in DMAV-exposed bladder urothelium and in DMAV-induced UCs in rats, suggest that these alterations occurred in the early stages of arsenic-induced bladder carcinogenesis. Further study to evaluate the functions of these genes will advance our understanding of the role of aberrant DNA methylation in arsenic bladder carcinogenesis, and will also facilitate the identification of new therapeutic targets for arsenic-related bladder cancers.

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Section: Introductionmentioning

confidence: 94%

DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis

Yamamoto,

Gi,

Yamashita

et al. 2023

Cancers

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“…To support the suggestion that DNA base oxidation might underly the mutagenic activity of arsenic they showed that under the same experimental conditions increased levels of 8‐oxoguanine are induced in the livers of arsenite‐exposed mice. A successive study (Fujioka et al., 2016 ) was unable to confirm the mutational activity of arsenic in vivo by analysing gpt mutations in urinary bladder epithelium and liver of rats exposed orally to similar arsenite doses for longer exposure times. This discrepancy might be explained by differences in iAs toxicokinetics between rats and mice (see Section 3.1.1.1 Metabolism).…”

Section: Assessmentmentioning

confidence: 99%

Update of the risk assessment of inorganic arsenic in food

Schrenk,

Bignami,

Bodin

et al. 2024

EFS2

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The European Commission asked EFSA to update its 2009 risk assessment on arsenic in food carrying out a hazard assessment of inorganic arsenic (iAs) and using the revised exposure assessment issued by EFSA in 2021. Epidemiological studies show that the chronic intake of iAs via diet and/or drinking water is associated with increased risk of several adverse outcomes including cancers of the skin, bladder and lung. The CONTAM Panel used the benchmark dose lower confidence limit based on a benchmark response (BMR) of 5% (relative increase of the background incidence after adjustment for confounders, BMDL05) of 0.06 μg iAs/kg bw per day obtained from a study on skin cancer as a Reference Point (RP). Inorganic As is a genotoxic carcinogen with additional epigenetic effects and the CONTAM Panel applied a margin of exposure (MOE) approach for the risk characterisation. In adults, the MOEs are low (range between 2 and 0.4 for mean consumers and between 0.9 and 0.2 at the 95th percentile exposure, respectively) and as such raise a health concern despite the uncertainties.

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Impact on growth, oxidative stress, and apoptosis-related gene transcription of zebrafish after exposure to low concentration of arsenite

et al. 2018

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Examination of in vivo mutagenicity of sodium arsenite and dimethylarsinic acid in gpt delta rats

Cited by 6 publications

References 35 publications

DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis

DNA Methylation Aberrations in Dimethylarsinic Acid-Induced Bladder Carcinogenesis

Update of the risk assessment of inorganic arsenic in food

Impact on growth, oxidative stress, and apoptosis-related gene transcription of zebrafish after exposure to low concentration of arsenite

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