cacodylic acid

Summary

Summary: An arsenical that has been used as a dermatologic agent and as an herbicide.

Top Publications

  1. Leffers L, Unterberg M, Bartel M, Hoppe C, Pieper I, Stertmann J, et al. In vitro toxicological characterisation of the S-containing arsenic metabolites thio-dimethylarsinic acid and dimethylarsinic glutathione. Toxicology. 2013;305:109-19 pubmed publisher
    ..Since in vivo RONS are permanently endogenously and exogenously produced, this boost of the existing oxidative stress by arsenite and thio-DMA(V) might contribute to the process of inorganic arsenic induced carcinogenicity...
  2. Schwerdtle T, Walter I, Mackiw I, Hartwig A. Induction of oxidative DNA damage by arsenite and its trivalent and pentavalent methylated metabolites in cultured human cells and isolated DNA. Carcinogenesis. 2003;24:967-74 pubmed
    ..Thus, biomethylation of inorganic arsenic may be involved in inorganic arsenic-induced genotoxicity/carcinogenicity. ..
  3. Wang Z, Zhou J, Lu X, Gong Z, Le X. Arsenic speciation in urine from acute promyelocytic leukemia patients undergoing arsenic trioxide treatment. Chem Res Toxicol. 2004;17:95-103 pubmed
    ..These results suggest that other pathways of excretion, such as through the bile, may play an important role in eliminating (removing) arsenic from the human body when challenged by high levels of As(III). ..
  4. Valenzuela O, Borja Aburto V, García Vargas G, Cruz Gonzalez M, García Montalvo E, Calderon Aranda E, et al. Urinary trivalent methylated arsenic species in a population chronically exposed to inorganic arsenic. Environ Health Perspect. 2005;113:250-4 pubmed
  5. Wei M, Wanibuchi H, Morimura K, Iwai S, Yoshida K, Endo G, et al. Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors. Carcinogenesis. 2002;23:1387-97 pubmed
    ..Furthermore, generation of ROS is likely to play an important role in the early stages of DMA carcinogenesis. ..
  6. Hsueh Y, Hsu M, Chiou H, Yang M, Huang C, Chen C. Urinary arsenic speciation in subjects with or without restriction from seafood dietary intake. Toxicol Lett. 2002;133:83-91 pubmed
    ..The frequencies of fish, shellfish and seaweed dietary intake were not significantly correlated with urinary arsenic species. ..
  7. Cohen S, Ohnishi T, Arnold L, Le X. Arsenic-induced bladder cancer in an animal model. Toxicol Appl Pharmacol. 2007;222:258-63 pubmed
    ..Extrapolation to human risk needs to take this into account along with the significant differences in toxicokinetics and toxicodynamics that occur between different species. ..
  8. Kenyon E, Hughes M, Adair B, Highfill J, Crecelius E, Clewell H, et al. Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water. Toxicol Appl Pharmacol. 2008;232:448-55 pubmed publisher
  9. Ahsan H, Chen Y, Kibriya M, Slavkovich V, Parvez F, Jasmine F, et al. Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in Bangladesh. Cancer Epidemiol Biomarkers Prev. 2007;16:1270-8 pubmed

More Information

Publications62

  1. Kenyon E, Hughes M. A concise review of the toxicity and carcinogenicity of dimethylarsinic acid. Toxicology. 2001;160:227-36 pubmed
    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 ..
  2. Naranmandura H, Ogra Y, Iwata K, Lee J, Suzuki K, Weinfeld M, et al. Evidence for toxicity differences between inorganic arsenite and thioarsenicals in human bladder cancer cells. Toxicol Appl Pharmacol. 2009;238:133-40 pubmed publisher
    ..In A431 cells, only mRNA and protein of AQP3 were detected. The large difference in toxicity between the two cell lines could be related to their differences in uptake of arsenic species...
  3. Hughes M, Del Razo L, Kenyon E. Dose-dependent effects on tissue distribution and metabolism of dimethylarsinic acid in the mouse after intravenous administration. Toxicology. 2000;143:155-66 pubmed
    ..No methylated or demethylated products of DMA were detected in blood or any organ up to 8 h post-exposure. The dose-dependent distribution of DMA in the lung may have a role in the toxic effects DMA elicits in this organ. ..
  4. He Y, Zheng Y. Assessment of in vivo bioaccessibility of arsenic in dietary rice by a mass balance approach. Sci Total Environ. 2010;408:1430-6 pubmed publisher
    ..Mass balance established during a controlled dietary experiment over 10 days is shown to be a useful approach to evaluate in vivo bioaccessibility and metabolism of arsenic uptake from diet and is applicable to study with more subjects. ..
  5. Naranmandura H, Ibata K, Suzuki K. Toxicity of dimethylmonothioarsinic acid toward human epidermoid carcinoma A431 cells. Chem Res Toxicol. 2007;20:1120-5 pubmed
  6. Yuan C, Lu X, Oro N, Wang Z, Xia Y, Wade T, et al. Arsenic speciation analysis in human saliva. Clin Chem. 2008;54:163-71 pubmed
    ..Determination of arsenic species in saliva is potentially useful for biomonitoring of human exposure and studying arsenic metabolism. Arsenic speciation in saliva has not been reported previously...
  7. Meza M, Kopplin M, Burgess J, Gandolfi A. Arsenic drinking water exposure and urinary excretion among adults in the Yaqui Valley, Sonora, Mexico. Environ Res. 2004;96:119-26 pubmed
    ..The difference in the proportion of urinary arsenic metabolites in those towns may be due to genetic polymorphisms in the As methylating enzymes of these populations. ..
  8. Hughes M, Kenyon E, Edwards B, Mitchell C, Razo L, Thomas D. Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Toxicol Appl Pharmacol. 2003;191:202-10 pubmed
    ..A trimethylated metabolite was also detected in the liver. Tissue accumulation of arsenic after repeated po exposure to arsenate in the mouse corresponds to the known human target organs for iAs-induced carcinogenicity. ..
  9. Ren X, Aleshin M, Jo W, Dills R, Kalman D, Vulpe C, et al. Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity. Environ Health Perspect. 2011;119:771-7 pubmed publisher
  10. Ochi T, Kita K, Suzuki T, Rumpler A, Goessler W, Francesconi K. Cytotoxic, genotoxic and cell-cycle disruptive effects of thio-dimethylarsinate in cultured human cells and the role of glutathione. Toxicol Appl Pharmacol. 2008;228:59-67 pubmed publisher
    ..These findings suggest that the presence of thio-DMA in human urine has implications for human health in terms of arsenic metabolism and toxicity. ..
  11. Wlodarczyk B, Spiegelstein O, Gelineau van Waes J, Vorce R, Lu X, Le C, et al. Arsenic-induced congenital malformations in genetically susceptible folate binding protein-2 knockout mice. Toxicol Appl Pharmacol. 2001;177:238-46 pubmed
  12. Bornhorst J, Ebert F, Lohren H, Humpf H, Karst U, Schwerdtle T. Effects of manganese and arsenic species on the level of energy related nucleotides in human cells. Metallomics. 2012;4:297-306 pubmed publisher
  13. Marapakala K, Qin J, Rosen B. Identification of catalytic residues in the As(III) S-adenosylmethionine methyltransferase. Biochemistry. 2012;51:944-51 pubmed publisher
    ..The rate-limiting step was identified as the conversion of DMAs(III) to trimethylarsine, and DMAs(III) accumulates as the principal product. ..
  14. Chen Y, Su H, Guo Y, Hsueh Y, Smith T, Ryan L, et al. Arsenic methylation and bladder cancer risk in Taiwan. Cancer Causes Control. 2003;14:303-10 pubmed
    ..39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels. ..
  15. Kitchin K, Ahmad S. Oxidative stress as a possible mode of action for arsenic carcinogenesis. Toxicol Lett. 2003;137:3-13 pubmed
    ..This would be particularly true for arsenate. In forming toxic and carcinogenic arsenic species, reduction from the pentavalent state to the trivalent state may be as or more important than methylation of arsenic. ..
  16. Huang Y, Huang Y, Hsueh Y, Yang M, Wu M, Chen S, et al. Arsenic exposure, urinary arsenic speciation, and the incidence of urothelial carcinoma: a twelve-year follow-up study. Cancer Causes Control. 2008;19:829-39 pubmed publisher
    ..There was a significant association between inefficient arsenic methylation and the development of UC in the residents in the high CAE exposure strata in an area of southwestern Taiwan endemic for arseniasis. ..
  17. Christian W, Hopenhayn C, Centeno J, Todorov T. Distribution of urinary selenium and arsenic among pregnant women exposed to arsenic in drinking water. Environ Res. 2006;100:115-22 pubmed
    ..The results of this study suggest that in populations exposed to arsenic, Se intake may be correlated with urinary As excretion, and may alter As methylation. ..
  18. Mandal B, Ogra Y, Suzuki K. Identification of dimethylarsinous and monomethylarsonous acids in human urine of the arsenic-affected areas in West Bengal, India. Chem Res Toxicol. 2001;14:371-8 pubmed
  19. Vega L, Styblo M, Patterson R, Cullen W, Wang C, Germolec D. Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Toxicol Appl Pharmacol. 2001;172:225-32 pubmed
  20. Heck J, Gamble M, Chen Y, Graziano J, Slavkovich V, Parvez F, et al. Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh. Am J Clin Nutr. 2007;85:1367-74 pubmed
    ..In particular, this study highlights the potential importance of dietary intakes of cysteine, methionine, niacin, vitamin B-12, and choline on health effects of arsenic by modulating its metabolism. ..
  21. Kuroda K, Yoshida K, Yoshimura M, Endo Y, Wanibuchi H, Fukushima S, et al. Microbial metabolite of dimethylarsinic acid is highly toxic and genotoxic. Toxicol Appl Pharmacol. 2004;198:345-53 pubmed
    ..Thus, we hypothesize that intestinal bacteria play an important role in carcinogenicity of dimethylarsinic acid. ..
  22. Bu N, Wang H, Hao W, Liu X, Xu S, Wu B, et al. Generation of thioarsenicals is dependent on the enterohepatic circulation in rats. Metallomics. 2011;3:1064-73 pubmed publisher
  23. Molin M, Ulven S, Dahl L, Telle Hansen V, Holck M, Skjegstad G, et al. Humans seem to produce arsenobetaine and dimethylarsinate after a bolus dose of seafood. Environ Res. 2012;112:28-39 pubmed publisher
  24. Loffredo C, Aposhian H, Cebrian M, Yamauchi H, Silbergeld E. Variability in human metabolism of arsenic. Environ Res. 2003;92:85-91 pubmed
    ..This analysis highlights the need for continuing research on the health effects of As in humans using molecular epidemiologic methods. ..
  25. McCarty K, Chen Y, Quamruzzaman Q, Rahman M, Mahiuddin G, Hsueh Y, et al. Arsenic methylation, GSTT1, GSTM1, GSTP1 polymorphisms, and skin lesions. Environ Health Perspect. 2007;115:341-5 pubmed
    ..The interaction between GSTT1 wildtype and secondary methylation ratio modifies risk of skin lesions among arsenic-exposed individuals. ..
  26. Raml R, Rumpler A, Goessler W, Vahter M, Li L, Ochi T, et al. Thio-dimethylarsinate is a common metabolite in urine samples from arsenic-exposed women in Bangladesh. Toxicol Appl Pharmacol. 2007;222:374-80 pubmed
    ..The work highlights the need for analytical methods providing specific determinations of arsenic compounds in future studies on arsenic metabolism and toxicology. ..
  27. Cohen S, Arnold L, Eldan M, Lewis A, Beck B. Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment. Crit Rev Toxicol. 2006;36:99-133 pubmed
    ..At anticipated environmental exposures to MMA(V) and DMA(V), there is not likely to be a carcinogenic risk to humans. ..
  28. Ahmad S, Kitchin K, Cullen W. Plasmid DNA damage caused by methylated arsenicals, ascorbic acid and human liver ferritin. Toxicol Lett. 2002;133:47-57 pubmed
    ..Addition of catalase (which can increase Fe(2+) concentrations) further increased the plasmid DNA damage. Iron-dependent DNA damage could be a mechanism of action of human arsenic carcinogenesis. ..
  29. Concha G, Vogler G, Nermell B, Vahter M. Intra-individual variation in the metabolism of inorganic arsenic. Int Arch Occup Environ Health. 2002;75:576-80 pubmed
    ..001) during the morning/day (03:00-15:00) compared with the evening/night (15:00-03:00). No within-day variation in the percentage of MMA was observed. The arsenic methylation efficiency of an individual is remarkably stable over time. ..
  30. Hansen H, Raab A, Jaspars M, Milne B, Feldmann J. Sulfur-containing arsenical mistaken for dimethylarsinous acid [DMA(III)] and identified as a natural metabolite in urine: major implications for studies on arsenic metabolism and toxicity. Chem Res Toxicol. 2004;17:1086-91 pubmed
    ..Dimethylarsinothioic acid was also identified as a metabolite in urine and in wool extract from sheep naturally consuming large amounts of arsenosugars (35 mg of As daily) through their major food source, seaweed. ..
  31. Nesnow S, Roop B, Lambert G, Kadiiska M, Mason R, Cullen W, et al. DNA damage induced by methylated trivalent arsenicals is mediated by reactive oxygen species. Chem Res Toxicol. 2002;15:1627-34 pubmed
    ..These data are consistent with the conclusions that the DNA-damaging activity of DMA(III) is an indirect genotoxic effect mediated by ROS-formed concomitantly with the oxidation of DMA(III) to DMA(V). ..
  32. Spiegelstein O, Lu X, Le X, Troen A, Selhub J, Melnyk S, et al. Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary speciation of sodium arsenate in mice. Toxicol Lett. 2003;145:167-74 pubmed
    ..The present data suggest that inadequate folate intake may result in decreased biotransformation and excretion of arsenic, which is likely to increase arsenic exposure and related toxicities. ..
  33. Gardner R, Nermell B, Kippler M, Grandér M, Li L, Ekström E, et al. Arsenic methylation efficiency increases during the first trimester of pregnancy independent of folate status. Reprod Toxicol. 2011;31:210-8 pubmed publisher
  34. Calatayud M, Vazquez M, Devesa V, Velez D. In vitro study of intestinal transport of inorganic and methylated arsenic species by Caco-2/HT29-MTX cocultures. Chem Res Toxicol. 2012;25:2654-62 pubmed publisher
    ..These results show the importance of choosing a suitable in vitro model when evaluating intestinal arsenic absorption processes. ..
  35. Jones M, Tellez Plaza M, Sharrett A, Guallar E, Navas Acien A. Urine arsenic and hypertension in US adults: the 2003-2008 National Health and Nutrition Examination Survey. Epidemiology. 2011;22:153-61 pubmed publisher
    ..A weak association of DMA with hypertension could not be ruled out. ..
  36. Gamble M, Liu X, Ahsan H, Pilsner R, Ilievski V, Slavkovich V, et al. Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect. 2005;113:1683-8 pubmed
    ..This may be particularly relevant in Bangladesh, where the prevalence of hyperhomocysteinemia is extremely high. ..
  37. Lindberg A, Goessler W, Grandér M, Nermell B, Vahter M. Evaluation of the three most commonly used analytical methods for determination of inorganic arsenic and its metabolites in urine. Toxicol Lett. 2007;168:310-8 pubmed
    ..Because of its considerably lower costs compared to HPLC-HG-ICPMS, it may be a good alternative in laboratories where the high cost of ICPMS is not justified in relation to the intended use of the instrument. ..
  38. Shiobara Y, Ogra Y, Suzuki K. Animal species difference in the uptake of dimethylarsinous acid (DMA(III)) by red blood cells. Chem Res Toxicol. 2001;14:1446-52 pubmed
    ..The present results suggest that the uptake of DMA by RBCs is an additional contributing factor to the animal species difference in the metabolism of arsenic in addition to the reduction and methylation capacity in the liver. ..
  39. Sakurai T, Qu W, Sakurai M, Waalkes M. A major human arsenic metabolite, dimethylarsinic acid, requires reduced glutathione to induce apoptosis. Chem Res Toxicol. 2002;15:629-37 pubmed
    ..These findings indicate that DMA likely is conjugated in some form with GSH, and that it is this conjugate that induces apoptosis during subsequent metabolic reactions. ..
  40. Nishikawa T, Wanibuchi H, Ogawa M, Kinoshita A, Morimura K, Hiroi T, et al. Promoting effects of monomethylarsonic acid, dimethylarsinic acid and trimethylarsine oxide on induction of rat liver preneoplastic glutathione S-transferase placental form positive foci: a possible reactive oxygen species mechanism. Int J Cancer. 2002;100:136-9 pubmed
    ..Since hydroxyradicals were found to be generated in the relatively early phase while methylated arsenicals were metabolized in liver, the resultant oxidative stress might have promoted lesion development. ..
  41. Cohen S, Arnold L, Uzvolgyi E, Cano M, St John M, Yamamoto S, et al. Possible role of dimethylarsinous acid in dimethylarsinic acid-induced urothelial toxicity and regeneration in the rat. Chem Res Toxicol. 2002;15:1150-7 pubmed
  42. Yoshida K, Kuroda K, Zhou X, Inoue Y, Date Y, Wanibuchi H, et al. Urinary sulfur-containing metabolite produced by intestinal bacteria following oral administration of dimethylarsinic acid to rats. Chem Res Toxicol. 2003;16:1124-9 pubmed
    ..M-2 was consistent with the reactant of DMAV with metabisulfite-thiosulfate reagent but not DMAIII by analyses of LC-ICP-MS and LC-MS. The molecular weight of M-2 was 154, and M-2 was a sulfur-containing metabolite. ..
  43. Xie Y, Trouba K, Liu J, Waalkes M, Germolec D. Biokinetics and subchronic toxic effects of oral arsenite, arsenate, monomethylarsonic acid, and dimethylarsinic acid in v-Ha-ras transgenic (Tg.AC) mice. Environ Health Perspect. 2004;112:1255-63 pubmed
    ..These effects may play a role in arsenic-induced hepatotoxicity and carcinogenesis and may be of particular toxicologic relevance. ..
  44. Suzuki K, Iwata K, Naranmandura H, Suzuki N. Metabolic differences between two dimethylthioarsenicals in rats. Toxicol Appl Pharmacol. 2007;218:166-73 pubmed
  45. Cascio C, Raab A, Jenkins R, Feldmann J, Meharg A, Haris P. The impact of a rice based diet on urinary arsenic. J Environ Monit. 2011;13:257-65 pubmed publisher
    ..Consequently, DMA/MA ratio as an indication of methylation capacity in populations consuming large quantities of rice should be applied with caution since variation in the quantity and type of rice eaten may alter this ratio. ..
  46. Calatayud M, Gimeno J, Velez D, Devesa V, Montoro R. Characterization of the intestinal absorption of arsenate, monomethylarsonic acid, and dimethylarsinic acid using the Caco-2 cell line. Chem Res Toxicol. 2010;23:547-56 pubmed publisher
    ..The results obtained constitute the basis for future research on the mechanisms involved in the intestinal absorption of arsenic and its species, a decisive step in relation to their toxic action...
  47. Salim E, Wanibuchi H, Morimura K, Wei M, Mitsuhashi M, Yoshida K, et al. Carcinogenicity of dimethylarsinic acid in p53 heterozygous knockout and wild-type C57BL/6J mice. Carcinogenesis. 2003;24:335-42 pubmed
    ..In conclusion, DMA primarily exerted its carcinogenic effect on spontaneous development of tumors with both of the animal genotypes investigated here. ..
  48. Calatayud M, Devesa V, Montoro R, Velez D. In vitro study of intestinal transport of arsenite, monomethylarsonous acid, and dimethylarsinous acid by Caco-2 cell line. Toxicol Lett. 2011;204:127-33 pubmed publisher
    ..Variations in pH do not affect transport of these species. The presence of GSH and green tea extract significantly alters transport of As(III) across Caco-2 cells...
  49. Tseng C, Huang Y, Huang Y, Chung C, Yang M, Chen C, et al. Arsenic exposure, urinary arsenic speciation, and peripheral vascular disease in blackfoot disease-hyperendemic villages in Taiwan. Toxicol Appl Pharmacol. 2005;206:299-308 pubmed
    ..05, trend test). It was concluded that individuals with a higher arsenic exposure and a lower capacity to methylate inorganic arsenic to DMA(V) have a higher risk of developing PVD in the BFD-hyperendemic area in Taiwan. ..
  50. Brooks M, Ravelli R, McCarthy A, Strub K, Cusack S. Structure of SRP14 from the Schizosaccharomyces pombe signal recognition particle. Acta Crystallogr D Biol Crystallogr. 2009;65:421-33 pubmed publisher
    ..The combination of SAD and RIP phases yielded an interpretable electron-density map. This example will be of general interest to crystallographers attempting de novo phasing from crystals grown in cacodylate buffer. ..
  51. Csanaky I, Gregus Z. Species variations in the biliary and urinary excretion of arsenate, arsenite and their metabolites. Comp Biochem Physiol C Toxicol Pharmacol. 2002;131:355-65 pubmed
    ..Thus, although the rat is not a good model for studying long-term arsenic disposition, this species appears especially valuable in studies on AsIII methyltransferase and in vivo formation of MMAsIII. ..
  52. Klein C, Leszczynska J, Hickey C, Rossman T. Further evidence against a direct genotoxic mode of action for arsenic-induced cancer. Toxicol Appl Pharmacol. 2007;222:289-97 pubmed
  53. Kawata H, Kuroda K, Endo Y, Inoue Y, Endo G. Simple and rapid determination of Gtpase activity by capillary electrophoresis without radioisotope. Tohoku J Exp Med. 2000;192:67-79 pubmed
    ..Thus, since this method is clean, simple and rapid, its application to the study of various GTPase proteins is expected to be useful. ..