Determination of trivalent methylated arsenicals in biological matrices

被引:216
作者
Del Razo, LM
Styblo, M
Cullen, WR
Thomas, DJ
机构
[1] US EPA, NHEERL, ORD, Pharmacokinet Branch,Expt Toxicol Div, Res Triangle Pk, NC 27711 USA
[2] Univ N Carolina, Sch Med, Ctr Environm Med & Lung Biol, Chapel Hill, NC 27599 USA
[3] Natl Polytech Inst, Ctr Res & Adv Studies, Sect Toxicol, Mexico City, DF, Mexico
[4] Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA
[5] Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC 27599 USA
[6] Univ British Columbia, Dept Chem, Vancouver, BC, Canada
关键词
arsenic; methylated arsenic; trivalent arsenic; pentavalent arsenic; hydride generation; atomic absorption spectrophotometry; analysis; stability; biological matrices; metabolism; toxicity;
D O I
10.1006/taap.2001.9226
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:282 / 293
页数:12
相关论文
共 67 条
[1]   EXTRACTION METHOD FOR ARSENIC SPECIATION IN MARINE ORGANISMS [J].
ALBERTI, J ;
RUBIO, R ;
RAURET, G .
FRESENIUS JOURNAL OF ANALYTICAL CHEMISTRY, 1995, 351 (4-5) :420-425
[2]  
American Public Health Association, 1989, STAND METH EX WAT WA
[3]   Occurrence of monomethylarsonous acid in urine of humans exposed to inorganic arsenic [J].
Aposhian, HV ;
Gurzau, ES ;
Le, XC ;
Gurzau, A ;
Healy, SM ;
Lu, XF ;
Ma, MS ;
Yip, L ;
Zakharyan, RA ;
Maiorino, RM ;
Dart, RC ;
Tircus, MG ;
Gonzalez-Ramirez, D ;
Morgan, DL ;
Avram, D ;
Aposhian, MM .
CHEMICAL RESEARCH IN TOXICOLOGY, 2000, 13 (08) :693-697
[4]   Enzymatic methylation of arsenic species and other new approaches to arsenic toxicity [J].
Aposhian, HV .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :397-419
[5]   DMPS -: Arsenic Challenge Test II.: Modulation of arsenic species, including monomethylarsonous acid (MMAIII), excreted in human urine [J].
Aposhian, HV ;
Zheng, BS ;
Aposhian, MM ;
Le, XC ;
Cebrian, ME ;
Cullen, W ;
Zakharyan, RA ;
Ma, HS ;
Dart, RC ;
Cheng, Z ;
Andrewes, P ;
Yip, L ;
O'Malley, GF ;
Maiorino, RM ;
Van Voorhies, W ;
Healy, SM ;
Titcomb, A .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2000, 165 (01) :74-83
[6]  
ARMIENTA MA, 1997, MEX HYDROGEOL, V5, P39
[7]   EPIDEMIOLOGIC STUDIES ON HUMAN-SUBJECTS EXPOSED TO ARSENIC IN DRINKING-WATER IN SOUTHEAST HUNGARY [J].
BORZSONYI, M ;
BERECZKY, A ;
RUDNAI, P ;
CSANADY, M ;
HORVATH, A .
ARCHIVES OF TOXICOLOGY, 1992, 66 (01) :77-78
[8]   Excretion of arsenic in urine as a function of exposure to arsenic in drinking water [J].
Calderon, RL ;
Hudgens, E ;
Le, XC ;
Schreinemachers, D ;
Thomas, DJ .
ENVIRONMENTAL HEALTH PERSPECTIVES, 1999, 107 (08) :663-667
[9]   Dose-response relationship between ischemic heart disease mortality and long-term arsenic exposure [J].
Chen, CJ ;
Chiou, HY ;
Chiang, MH ;
Lin, LJ ;
Tai, TY .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (04) :504-510
[10]   Dose-response relationship between prevalence of cerebrovascular disease and ingested inorganic arsenic [J].
Chiou, HY ;
Huang, WI ;
Su, CL ;
Chang, SF ;
Hsu, YH ;
Chen, CJ .
STROKE, 1997, 28 (09) :1717-1723