@article {5045,
	title = {Determination of trivalent methylated arsenicals in biological matrices},
	journal = {Toxicology and Applied Pharmacology},
	volume = {174},
	number = {3},
	year = {2001},
	note = {ISI Document Delivery No.: 464KTTimes Cited: 129Cited Reference Count: 67},
	month = {Aug},
	pages = {282-293},
	type = {Article},
	abstract = {The enzymatically catalyzed oxidative methylation of As yields methylated arsenicals that contain pentavalent As (As-V). Because trivalent As (As-III) is the favored substrate for this methyltransferase, methylated arsenicals containing As-V are reduced to trivalency in cells. Methylated arsenicals that contain As-III are extremely potent inhibitors of NADPH-dependent flavoprotein oxidoreductases and potent cytotoxins in many cell types. Therefore, the formation of methylated arsenicals that contain As-III may be properly regarded as an activation step, rather than a means of detoxification. Recognition of the role of methylated arsenicals that contain As-III in the toxicity and metabolism of As emphasizes the need for analytical methods to detect and quantify these species in biological samples. Hence, a method was developed to exploit pH-dependent differences in the generation of arsines from inorganic and methylated arsenicals that contain either As-V or As-III. Reduction with borohydride at pH 6 generated arsines from inorganic As-III, methyl As-III, and dimethyl As-III, but not from inorganic As-V, methyl As-V, and dimethyl As-V. Reduction with borohydride at pH 2 or lower generated arsines from arsenicals that contained either As-V or As-III. Arsines are trapped in a liquid nitrogen-cooled gas chromatographic trap, which is subsequently warmed to allow separation of the hydrides by their boiling points. Atomic absorption spectrophotometry is used to detect and quantify the arsines. The detection limits (ng As ml(-1)) for inorganic As-III, methyl As-III, and dimethyl As-III are 1.1, 1.2, and 6.5, respectively. This method has been applied to the analysis of arsenicals in water, human urine, and cultured cells. Both methyl As-III. and dimethyl As-III are detected in urine samples from individuals who chronically consumed inorganic As-contaminated water and in human cells exposed in vitro to inorganic As-III. The reliable quantitation of inorganic and methylated arsenicals that contain As-III. in biological samples will aid the study of the toxicity of these species and may provide a new biomarker of the effects of chronic exposure to As. (C) 2001 Academic Press.},
	keywords = {analysis, arsenic, atomic absorption spectrophotometry, biological matrices, CANCER MORTALITY, DIABETES-MELLITUS, DIMETHYLARSINIC ACID, DOSE-RESPONSE RELATIONSHIP, DRINKING-WATER, ENZYMATIC, HUMAN URINE, HYDRIDE GENERATION, MAMMALIAN SYSTEMS, MASS-SPECTROMETRY, METABOLISM, methylated arsenic, METHYLATION, MONOMETHYLARSONOUS ACID MMA(III), pentavalent arsenic, STABILITY, TOXICITY, trivalent arsenic},
	isbn = {0041-008X},
	url = {<Go to ISI>://000170532300010},
	author = {Del Razo, L. M. and Styblo, M. and Cullen, W. R. and Thomas, D. J.}
}
