Arsenic toxicity and potential mechanisms of action

被引:1285
作者
Hughes, MF [1 ]
机构
[1] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA
关键词
arsenic; toxicity; mechanisms;
D O I
10.1016/S0378-4274(02)00084-X
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Exposure to the metalloid arsenic is a daily occurrence because of its environmental pervasiveness. Arsenic, which is found in several different chemical forms and oxidation states, causes acute and chronic adverse health effects, including cancer. The metabolism of arsenic has an important role in its toxicity. The metabolism involves reduction to a trivalent state and oxidative methylation to a pentavalent state. The trivalent arsenicals, including those methylated, have more potent toxic properties than the pentavalent arsenicals. The exact mechanism of the action of arsenic is not known, but several hypotheses have been proposed. At a biochemical level, inorganic arsenic in the pentavalent state may replace phosphate in several reactions. In the trivalent state, inorganic and organic (methylated) arsenic may react with critical thiols in proteins and inhibit their activity. Regarding cancer, potential mechanisms include genotoxicity, altered DNA methylation, oxidative stress, altered cell proliferation, co-carcinogenesis, and tumor promotion. A better understanding of the mechanism(s) of action of arsenic will make a more confident determination of the risks associated with exposure to this chemical. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:1 / 16
页数:16
相关论文
共 136 条
[1]  
ADKINSON DL, 1991, VET PATHOL, V22, P305
[2]   Arsenic species that cause release of iron from ferritin and generation of activated oxygen [J].
Ahmad, S ;
Kitchin, KT ;
Cullen, WR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2000, 382 (02) :195-202
[3]  
[Anonymous], 1999, Arsenic in drinking water
[4]   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
[5]  
Aposhian HV., 1989, REV BIOCH TOXICOLOGY, P265
[6]   Effects of dietary dimethylarsinic acid on the urine and urothelium of rats [J].
Arnold, LL ;
Cano, M ;
St John, M ;
Eldan, M ;
van Gemert, M ;
Cohen, SM .
CARCINOGENESIS, 1999, 20 (11) :2171-2179
[7]   Gene expression and the thiol redox state [J].
Arrigo, AP .
FREE RADICAL BIOLOGY AND MEDICINE, 1999, 27 (9-10) :936-944
[8]   CASE-CONTROL STUDY OF BLADDER-CANCER AND ARSENIC IN DRINKING-WATER [J].
BATES, MN ;
SMITH, AH ;
CANTOR, KP .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1995, 141 (06) :523-530
[9]  
Bencko V., 1978, IND ENV XENOBIOTICS, P312
[10]   SYMPOSIUM - CELLULAR-RESPONSE TO DNA DAMAGE - THE ROLE OF POLY(ADP-RIBOSE) - POLY(ADP-RIBOSE) IN THE CELLULAR-RESPONSE TO DNA DAMAGE [J].
BERGER, NA .
RADIATION RESEARCH, 1985, 101 (01) :4-15