Arsenicals affect base excision repair by several mechanisms

Ebert, Franziska; Weiss, André; Bültemeyer, Milena; Hamann, Ingrit; Hartwig, Andrea; Schwerdtle, Tanja

doi:10.1016/j.mrfmmm.2011.07.004

Cited by 89 publications

(75 citation statements)

References 59 publications

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“…DMA (V) has shown genotoxic effects on cultured mammalian cells [115,124], and in animal studies been reported to promote carcinogenic effects in the urinary bladder, kidney, liver and the thyroid gland [125,126]. Both MA (V) and DMA (V) has been classified as "possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer (IARC) [127].…”

Section: Mechanisms and Toxicity Of Arsenic Compounds Occurring In Sementioning

confidence: 99%

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

Molin

Ulven

Meltzer

et al. 2015

Journal of Trace Elements in Medicine and Biology

196

105

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Section: Mechanisms and Toxicity Of Arsenic Compounds Occurring In Sementioning

confidence: 99%

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

Molin

Ulven

Meltzer

et al. 2015

Journal of Trace Elements in Medicine and Biology

196

105

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“…Studies on the relationship between environmental factors and 8-OH-dG generation pointed out that OGG1 downregulation or inhibition of the enzyme activity appears as a common mechanism of action (Hirano 2008). As for arsenic compounds, their ability of inhibiting the 8-OH-dG repair capacity has been extensively reported, at least within the acute range of exposure (Ebert et al 2011;Hirano 2008).…”

Section: Introductionmentioning

confidence: 99%

Oxidative DNA damage enhances the carcinogenic potential of in vitro chronic arsenic exposures

et al. 2015

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Chronic exposure to arsenic is known to increase the incidence of cancer in humans. Our previous work demonstrated that environmentally relevant arsenic exposures generate an accelerated accumulation of pre-carcinogen 8-OH-dG DNA lesions under Ogg1-deficient backgrounds, but it remains unproved whether this observed arsenic-induced oxidative DNA damage (ODD) is certainly important in terms of cancer. Here, isogenic MEF Ogg1 (+/+) cells and MEF Ogg1 (-/-) cells-unable to properly eliminate 8-OH-dG from DNA-were exposed to 0.5, 1 and 2 µM of sodium arsenite for 40 weeks. The acquisition of an in vitro cancer-like phenotype was assessed throughout the exposure; matrix metalloproteinase (MMP) activities were measured by zymography, colony formation and promotion were evaluated by soft agar assay, and cellular invasiveness was measured by the transwell assay. Alterations in cellular morphology, growth and differentiation status were also included as complementary measures of transformation. MEF Ogg1 (-/-) cells showed a cancer-associated phenotype after 30 weeks of exposure, as indicated by morphological changes, increased proliferation, deregulated differentiation status, increased MMPs secretion, anchorage-independent cell growth and enhancement of tumor growth and invasiveness. Conversely, MEF Ogg1 (+/+) cells did not present changes in morphology or proliferation, exhibited a milder degree of gene deregulation and needed 10 weeks of additional exposure to the highest arsenite doses to show tumor enhancing effects. Thus, Ogg1 genetic background and arsenic-induced 8-OH-dG proved relevant for arsenic-mediated carcinogenic effects. To our knowledge, this is the first study directly linking ODD with arsenic carcinogenesis.

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“…Cell number and colony forming ability testing were performed as described before [26]. Briefly, after 24 h of incubation with the respective arsenicals, cells were washed with phosphate buffered saline (PBS) and trypsinised.…”

Section: Cytotoxicity Testingmentioning

confidence: 99%

“…Briefly, 24 h after seeding, cells were incubated with the respective arsenic species for 24 h. All further steps were performed exactly as described before [26]. Primer sequences are shown in Table 1.…”

Section: Caspase-3 Activationmentioning

confidence: 99%

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

Ebert

Leffers

Weber

et al. 2014

Journal of Trace Elements in Medicine and Biology

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Thio-dimethylarsinic acid (thio-DMA(V)) has recently been identified as human metabolite after exposure toward both the human carcinogen inorganic arsenic and arsenosugars, which are the major arsenical constituents of marine algae. This study aims to get further insight in the toxic modes of action of thio-DMA(V) in cultured human urothelial cells. Among others effects of thio-DMA(V) on eight cell death related endpoints, cell cycle distribution, genotoxicity, cellular bioavailability as well as for the first time its impact on DNA damage induced poly(ADP-ribosyl)ation were investigated and compared to effects induced by arsenite. The data indicate that thio-DMA(V) exerts its cellular toxicity in a similar or even lower concentration range, however most likely via different mechanisms, than arsenite. Most interestingly, thio-DMA(V) decreased damage-induced cellular poly(ADP-ribosyl)ation by 35,000-fold lower concentrations than arsenite. The inhibition of this essential DNA-damage induced and DNA-repair related signaling reaction might contribute to inorganic arsenic induced toxicity, at least in the bladder. Therefore, and also because thio-DMA(V) is to date by far the most toxic human metabolite identified after arsenosugar intake, thio-DMA(V) should contemporary be fully (also in vivo) toxicologically characterized, to assess risks to human health related to inorganic arsenic but especially arsenosugar dietary intake.

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Arsenicals affect base excision repair by several mechanisms

Cited by 89 publications

References 59 publications

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

Arsenic in the human food chain, biotransformation and toxicology – Review focusing on seafood arsenic

Oxidative DNA damage enhances the carcinogenic potential of in vitro chronic arsenic exposures

Toxicological properties of the thiolated inorganic arsenic and arsenosugar metabolite thio-dimethylarsinic acid in human bladder cells

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