The Role of Biomethylation in Toxicity and Carcinogenicity of Arsenic: A Research Update

Stýblo, Miroslav; Drobná, Zuzana; Jaspers, Ilona; Lin, Shu; Thomas, David J.

doi:10.1289/ehp.02110s5767

Cited by 233 publications

(141 citation statements)

References 30 publications

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“…Biomethylation is the major metabolic process for inorganic arsenic (27)(28)(29)(30). The stepwise methylation process is believed to involve a sequence of a two-electron reduction of arsenic followed by the oxidative addition of a methyl group (31).…”

Section: Inorganic Arsenicmentioning

confidence: 99%

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Peer Reviewed: Arsenic Speciation

Le¹,

Lu²,

Li³

2004

Anal. Chem.

142

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Section: Inorganic Arsenicmentioning

confidence: 99%

“…Although arsenic in drinking water affects millions of people worldwide, the physiological mechanisms are not known (4,30,37,38). Understanding arsenic binding to proteins may provide useful insight.…”

Section: Understanding Arsenic's Health Effectsmentioning

confidence: 99%

Peer Reviewed: Arsenic Speciation

Le¹,

Lu²,

Li³

2004

Anal. Chem.

142

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“…Until recently inorganic arsenic, 25 particularly As III , was considered the most toxic chemical form with the methylation of inorganic arsenic considered a detoxification step. There is now strong evidence to suggest that the methylation of arsenic is a process that activates arsenic as both a toxin and carcinogen 23,24 . Therefore the 30 identification of As speciation in toenails may be useful in understanding the potential toxicity of ingested arsenic.…”

mentioning

confidence: 99%

Human toenails as a biomarker of exposure to elevated environmental arsenic

et al. 2009

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A pilot study was conducted to determine the applicability of toenails as a biomarker of exposure to elevated environmental arsenic (As) levels. A total of 17 individuals were recruited for the pilot study: 8 residents living near to a former As mine, Devon, UK, forming the exposed group, plus 9 10 residents from Nottinghamshire, UK, with no anticipated As exposure who were used for comparison as a control group. All toenail samples were thoroughly washed prior to analysis and the wash solutions retained for As determination via ICP-MS to provide an indication of the background environmental As levels for each group. Total As was determined in washed toenail samples via ICP-MS following microwave assisted acid digestion. Concentrations of total As in the 15 toenails of the exposed group were elevated, ranging from 858 to 25,981 µg kg -1 (geometric mean = 5406 µg kg -1 ), compared to the control group whose toenail As concentrations ranged from 73 to 273 µg kg -1 (geometric mean = 122 µg kg -1 ). Higher levels of exogenous As contamination were present on the toenails of the exposed group (geometric mean = 506 µg kg -1 ) compared to the control group (geometric mean = 4.0 µg kg -1 ) providing evidence of higher environmental As 20 levels in the exposed group. Total As concentrations in toenail samples were positively correlated to environmental As levels (r = 0.60, p <0.001). HPLC-ICP-MS analysis of aqueous toenail extracts revealed inorganic arsenite (As III ) to be the dominant species extracted (~ 83 %) with lesser amounts of inorganic arsenate (As V ) and organic dimethylarsinate (DMA V ) at ~ 13 % and ~ 8.5 % respectively. Arsenic speciation in analysed toenail extracts from the two groups was 25 comparable. The only notable difference between groups was the presence of small amounts (<1 %) of organic methylarsonate (MA V ) in two toenail samples from the exposed group. Toenails are presented as a viable biomarker of exposure at sites with elevated environmental As, such as the former mining sites found throughout Devon and Cornwall, UK. Introduction 30Arsenic is naturally occurring and ubiquitous in the environment. Humans are exposed to As via contaminated water, food, soil and dust 1 . Chronic exposure to As is associated with increases in lung, liver, bladder and kidney cancer, skin keratoses and peripheral vascular disease 2, 3 . 35 Biological markers (biomarkers) can be utilised to make quantitative estimates of exposure to harmful substances 4 and subsequent risk of disease. There is now increasing interest in the use of human nails as a routine biomarker of As exposure. On ingestion, soluble arsenic is adsorbed from the gastro- 40 intestinal tract and distributed to all bodily systems in the blood, accumulating in many body parts, in particular the keratin rich materials such as hair and nails 5 . Arsenic is thought to accumulate in hair and nails as a result of its affinity for sulphydryl groups 6 and remains isolated from the 45 body's metabolic processes both after nail formation and througho...

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“…The column effluent was directly introduced into the nebulizer rod of the ICP-MS equipment by a polytetrafluoroethylene capillary tube of dimension 250 mm × 0.5 mm (id). The ion intensity at m/z of 75 As was monitored, but an important interference during ICP-MS analysis is the possible formation of 40 Ar 35 Cl, however chloride concentrations in the analyzed fractions were low and the eventual interference was corrected by the correction factor introduced in the operational software of the instrument. The chromatographic peaks were integrated using the software ICP-MS Plasma Lab and Captures Grams/32 (Galactic Industries Salem NY, USA).…”

Section: Hplc -Icp -Ms For As Speciesmentioning

confidence: 99%

“…Therefore, before methylation, increases the in vivo toxicity and risk to the organism 39 . Otherwise, recently has been informed that biomethylation being a process that potentiates toxicity and carcinogenicity of inorganic As 40 .…”

Section: Introductionmentioning

confidence: 99%

TOTAL AND MAIN As SPECIES PRESENT IN CARDIOVASCULAR TISSUES OF PEOPLE LIVINGIN As CONTAMINATED AREAS

Pizarro

Roman-Silva

Solar³

et al. 2012

J. Chil. Chem. Soc.

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The concentration levels of As in the Chilean II Region of Antofagasta produces non cancer health outcomes such as cardiovascular diseases and in last term heart attack. On this study, the determination of total As content and main inorganic and organoarsenic species found in three heart tissues (auricle, mammary artery and fat) and the saphene vein of people living in the Chilean II Region, suffering coronary thrombosis has been carried out. Comparison with similar tissues of patients from other non-contaminated areas has been undertaken.The extraction of As species occurred in methanol: water (1:1) and As species determination have been used the tandem HPLC-ICP-MS using the Hamilton PRP X100 anion column. For total As determination has been performed by HG-AAS and ICP-MS.The auricle and in less extend the saphene support the higher As concentration (mean values of 7.7 and 2.5 µg g -1 , respectively), being As(III) the predominant species. Methylarsonate (MA) and dimethylarsinate (DMA) is not a favoured mechanism.The presence of high total As and high As(III) species content in the auricle and saphene of more contaminated people, the damage found in the saphene tissue and the global characteristics of the people under study in which the As stigmas are present in all of them, suggests that As could be involved in the cardiovascular diseases.

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The Role of Biomethylation in Toxicity and Carcinogenicity of Arsenic: A Research Update

Cited by 233 publications

References 30 publications

Peer Reviewed: Arsenic Speciation

Peer Reviewed: Arsenic Speciation

Human toenails as a biomarker of exposure to elevated environmental arsenic

TOTAL AND MAIN As SPECIES PRESENT IN CARDIOVASCULAR TISSUES OF PEOPLE LIVINGIN As CONTAMINATED AREAS

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