Toxicity of arsenite and thio-DMA<sup>V</sup> after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics

Unterberg, Marlies; Leffers, Larissa; Hübner, Florian; Humpf, Hans‐Ulrich; Lepikhov, Konstantin; Walter, Jörn; Ebert, Franziska; Schwerdtle, Tanja

doi:10.1039/c4tx00036f

Cited by 10 publications

(11 citation statements)

References 57 publications

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“…Thio-DMA(V) showed no genotoxic mode of action in lung cells (Bartel et al 2011), but DNA damage and changes in gene expression were observed in bladder cells exposed to this compound (Naranmandura et al 2011); most recently a disturbance of the cellular damage response in DNA-damaged bladder cells was observed at sub-cytotoxic levels (Ebert et al 2014). Epigenetic effects from longterm exposure to thio-DMA(V) have also been observed at low picomolar levels (Unterberg et al 2014). …”

Section: 0 Toxicitymentioning

confidence: 99%

Human exposure to organic arsenic species from seafood

Taylor

Goodale

Raab

et al. 2017

Science of The Total Environment

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383

256

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Seafood, including finfish, shellfish, and seaweed, is the largest contributor to arsenic (As) exposure in many human populations. In contrast to the predominance of inorganic As in water and many terrestrial foods, As in marine-derived foods is present primarily in the form of organic compounds. To date, human exposure and toxicological assessments have focused on inorganic As, while organic As has generally been considered to be non-toxic. However, the high concentrations of organic As in seafood, as well as the often complex As speciation, can lead to complications in assessing As exposure from diet. In this report, we evaluate the presence and distribution of organic As species in seafood, and combined with consumption data, address the current capabilities and needs for determining human exposure to these compounds. The analytical approaches and shortcomings for assessing these compounds are reviewed, with a focus on the best practices for characterization and quantitation. Metabolic pathways and toxicology of two important classes of organic arsenicals, arsenolipids and arsenosugars, are examined, as well as individual variability in absorption of these compounds. Although determining health outcomes or assessing a need for regulatory policies for organic As exposure is premature, the extensive consumption of seafood globally, along with the preliminary toxicological profiles of these compounds and their confounding effect on assessing exposure to inorganic As, suggests further investigations and process-level studies on organic As are needed to fill the current gaps in knowledge.

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Section: 0 Toxicitymentioning

confidence: 99%

Human exposure to organic arsenic species from seafood

Taylor

Goodale

Raab

et al. 2017

Science of The Total Environment

Self Cite

383

256

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“…Thio-DMA V has been observed as a product of both iAs and AsSugar metabolism. , Considerable toxicity from thio-DMA V has been witnessed in skin, bladder, liver, and lung cells, which is partly linked to its extreme cellular bioavailability. − Thio-DMA V has been proven to generate ROS in healthy cells − and to disturb cellular stress response, even at picomolar levels, in oxidatively stressed cells. − Thio-DMA V exhibited no genotoxic mode of action in lung cells, but DNA injury and alterations in gene expression were witnessed in bladder cells exposed to such species . Epigenetic effects from long-term exposure to thio-DMA V have also been detected at low picomolar levels …”

Section: Metabolic Transformation and Toxicity Of Arsenicmentioning

confidence: 99%

“…176 Epigenetic effects from long-term exposure to thio-DMA V have also been detected at low picomolar levels. 180 2.7. Arsenosugars (AsSugars).…”

Section: Metabolic Transformation and Toxicitymentioning

confidence: 99%

Organoarsenicals in Seafood: Occurrence, Dietary Exposure, Toxicity, and Risk Assessment Considerations – A Review

Luvonga

Rimmer

et al. 2020

J. Agric. Food Chem.

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Diet, especially seafood, is the main source of arsenic exposure for humans. The total arsenic content of a diet offers inadequate information for assessment of the toxicological consequences of arsenic intake, which has impeded progress in the establishment of regulatory limits for arsenic in food. Toxicity assessments are mainly based on inorganic arsenic, a well-characterized carcinogen, and arsenobetaine, the main organoarsenical in seafood. Scarcity of toxicity data for organoarsenicals, and the predominance of arsenobetaine as an organic arsenic species in seafood, has led to the assumption of their nontoxicity. Recent toxicokinetic studies show that some organoarsenicals are bioaccessible and cytotoxic with demonstrated toxicities like that of pernicious trivalent inorganic arsenic, underpinning the need for speciation analysis. The need to investigate and compare the bioavailability, metabolic transformation, and elimination from the body of organoarsenicals to the well-established physiological consequences of inorganic arsenic and arsenobetaine exposure is apparent. This review provides an overview of the occurrence and assessment of human exposure to arsenic toxicity associated with the consumption of seafood.

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“…It is already known that DMA 5+ is the major human urinary metabolite following both inorganic arsenic exposure and dietary arsenosugar exposure [ 32 ]; the literature implies perhaps the same premise for thio-DMA and possibly other thio-arsenicals being metabolites following both inorganic exposure or dietary arsenosugar exposure. This will be of some concern as toxicological studies have shown thio-DMA to be genotoxic, cytotoxic and as toxic or more cytotoxic than arsenite in studies with rats [ 33 , 34 ], human bladder cells [ 23 , 35 , 36 ] and human lung cells [ 37 , 38 , 39 ], with one study describing thio-DMA as “one of the most toxicologically potent arsenic species, relevant to arsenic induced carcinogenicity” [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

Leese

Clench

Morton

et al. 2017

Toxics

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This study investigates the identity of two unexpected arsenic species found separately in a number of urine samples sent to the Health and Safety Executive’s Health and Safety Laboratory for arsenic speciation (arsenobetaine, AB; arsenite, As3+; arsenate, As5+; monomethylarsonic acid, MMA5+; and dimethylarsinic acid, DMA5+). Micro liquid chromatography coupled to inductively coupled plasma mass spectrometry (µLC-ICP-MS) and electrospray time of flight tandem mass spectrometry (ESI-QqTOF-MS/MS) were used to identify the two arsenic peaks by comparison to several characterized arsenicals: arsenocholine, AC; trimethyl arsine oxide, TMAO; dimethylarsenoacetate, DMAA; dimethylarsenoethanol, DMAE; thio-dimethylarsinate, thio-DMA; thio-dimethylarsenoacetate, thio-DMAA and thio-dimethylarsenoethanol, thio-DMAE. The results from both the ICP-MS and ESI-QqTOF-MS/MS investigations indicate that the unexpected arsenic species termed peak 1 was thio-DMA. While the unexpected arsenic species termed peak 2 has yet to be identified, this investigation shows that it was not AC, TMAO, DMAA, DMAE, thio-DMA, thio-DMAA or thio-DMAE. This study demonstrates the incidence of unexpected arsenic species in both routine and non-routine urine samples from both workers and hospital patients.

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Toxicity of arsenite and thio-DMA^V after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics

Abstract: This study aims to further mechanistically understand toxic modes of action after chronic arsenic species exposure.

Cited by 10 publications

References 57 publications

Human exposure to organic arsenic species from seafood

Human exposure to organic arsenic species from seafood

Organoarsenicals in Seafood: Occurrence, Dietary Exposure, Toxicity, and Risk Assessment Considerations – A Review

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

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Toxicity of arsenite and thio-DMAV after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics

Abstract: This study aims to further mechanistically understand toxic modes of action after chronic arsenic species exposure.

Cited by 10 publications

References 57 publications

Human exposure to organic arsenic species from seafood

Human exposure to organic arsenic species from seafood

Organoarsenicals in Seafood: Occurrence, Dietary Exposure, Toxicity, and Risk Assessment Considerations – A Review

The Investigation of Unexpected Arsenic Compounds Observed in Routine Biological Monitoring Urinary Speciation Analysis

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Product

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Toxicity of arsenite and thio-DMA^V after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics