Mutagenicity of dimethylated metabolites of inorganic arsenics.

Yamanaka, Kazuhiro; Ohba, Hiroshi; Hasegawa, Akira; Sawamura, Ryoji; Okada, Shoji

doi:10.1248/cpb.37.2753

Cited by 43 publications

(27 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, it has also been postulated that an increase in DMA may be more deleterious than previously thought. In vitro studies found that DMA can cause chromosomal damage (46,47); similar studies were not reported for MMA. A recent report of the study in Mexico indicated that exposed individuals with skin alterations had a higher MMA:DMA ratio than exposed persons without skin effects (34).…”

Section: Discussionmentioning

confidence: 72%

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 72%

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Hopenhayn‐Rich¹,

Biggs²,

Smith³

et al. 1996

Environmental Health Perspectives

View full text Add to dashboard Cite

“…10 mM (Yamanaka et al, 1989c). Experiments indicated that a methylated arsine metabolite was formed, and because the mutagenic effect required the presence of oxygen, it was suggested that a reactive species formed from the reaction of dimethylarsine and oxygen, perhaps a peroxyl radical, may be the ultimate mutagenic metabolite.…”

Section: Cytotoxicity and Genotoxicitymentioning

confidence: 99%

A concise review of the toxicity and carcinogenicity of dimethylarsinic acid

2001

View full text Add to dashboard Cite

Dimethylarsinic acid (DMA) has been used as a herbicide (cacodylic acid) and is the major metabolite formed after exposure to tri-(arsenite) or pentavalent (arsenate) inorganic arsenic (iAs) via ingestion or inhalation in both humans and rodents. Once viewed simply as a detoxification product of iAs, evidence has accumulated in recent years indicating that DMA itself has unique toxic properties. DMA induces an organ-specific lesion -single strand breaks in DNA -in the lungs of both mice and rats and in human lung cells in vitro. Mechanistic studies have suggested that this damage is due mainly to the peroxyl radical of DMA and production of active oxygen species by pulmonary tissues. Multi-organ initiation-promotion studies have demonstrated that DMA acts as a promotor of urinary bladder, kidney, liver and thyroid gland cancers in rats and as a promotor of lung tumors in mice. Lifetime exposure to DMA in diet or drinking water also causes a dose-dependent increase in urinary bladder tumors in rats, indicating that DMA is a complete carcinogen. These data collectively suggest that DMA plays a role in the carcinogenesis of inorganic arsenic. Published by Elsevier Science Ireland Ltd.Keywords: Arsenic; Cancer; Dimethylarsinic acid www.elsevier.com/locate/toxicol Dimethylarsinic acid 1 (DMA; see Fig. 1) has been used as a herbicide and is also the major metabolite formed after exposure to trivalent (arsenite, AsIII) or pentavalent (arsenate, AsV) inorganic arsenic via ingestion or inhalation in both humans and most rodents (US EPA, 1975; ATSDR, 1993). Methylation of inorganic arsenic to form both DMA and methylarsonic acid (MMA) has traditionally been viewed as a mechanism to facilitate the detoxification and excretion of arsenic. This is principally because DMA, in particular, is over 10-fold less acutely toxic than inorganic arsenic (Kaise et al., 1985(Kaise et al., , 1989. However, evidence suggesting that DMA itself has unique toxic properties has accumulated in the * Corresponding author. Tel.: +1-919-5410043; fax: +1-919-5415394.E-mail address: kenyon.elaina@epa.gov (E.M. Kenyon). 1 Unless specifically stated otherwise, the abbreviation DMA refers to pentavalent dimethyl form of arsenic. The distinction is important because emerging evidence suggests that both trivalent monomethylated arsenic and trivalent DMA are more tissue-reactive and cytotoxic than their pentavalent counterparts.0300-483X/01/$ -see front matter Published by Elsevier Science Ireland Ltd. PII: S 0 3 0 0 -4 8 3 X ( 0 0 ) 0 0 4 5 8 -3

show abstract

“…''.I4 DMA induces tetraploids and mitotic arrest in Chinese hamster cell^,'^ and causes DNA damage in mice. 16 A few studies on the metabolism of DMA have been conducted but there have been no reports concerning chronic exposure to DMA. On the other hand, the effects of arsenic on humans are often due to chronic exposure.…”

Section: Ntrod Uctlonmentioning

confidence: 99%

Methylation and Demethylation of Dimethylarsinic Acid in Rats Following Chronic Oral Exposure

Chen

Yoshida

Wanibuchi

et al. 1996

Appl. Organometal. Chem.

View full text Add to dashboard Cite

Metabolites of dimethylarsinic acid (DMA) were studied in rats chronically exposed to DMA in drinking water. The urine was collected by forced urination at the end of 8, 20 and 30 weeks and the feces at the end of 30 weeks. The samples were analyzed for arsenic species by a combined system of ion chromatography and inductively coupled plasma mass spectrometry (IC–ICP–MS). Increases in arsenite, DMA, trimethylarsine oxide and a still‐to‐be‐identified arsenic compound (which was eluted immediately after monomethylarsonic acid on the chromatogram) were detected in both urine and feces. At the 100 mg l−1 dose, DMA was the main component in the urine; arsenite was a main component in the feces. The results indicate that, besides undergoing methylation, DMA can be demethylated to inorganic arsenic, and demethylation of DMA may be associated with intestinal bacteria

show abstract

Mutagenicity of dimethylated metabolites of inorganic arsenics.

Cited by 43 publications

References 1 publication

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

Methylation Study of a Population Environmentally Exposed to Arsenic in Drinking Water

A concise review of the toxicity and carcinogenicity of dimethylarsinic acid

Methylation and Demethylation of Dimethylarsinic Acid in Rats Following Chronic Oral Exposure

Contact Info

Product

Resources

About