Arsenic Exposure and Toxicology: A Historical Perspective
Top Cited Papers
Open Access
- 12 July 2011
- journal article
- review article
- Published by Oxford University Press (OUP) in Toxicological Sciences
- Vol. 123 (2), 305-332
- https://doi.org/10.1093/toxsci/kfr184
Abstract
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.Keywords
This publication has 275 references indexed in Scilit:
- Association of genetic variation in cystathionine-β-synthase and arsenic metabolismEnvironmental Research, 2010
- Influence of arsenate and arsenite on signal transduction pathways: an updateArchives of Toxicology, 2010
- Association of AS3MT polymorphisms and the risk of premalignant arsenic skin lesionsToxicology and Applied Pharmacology, 2009
- Activation of Nrf2 by arsenite and monomethylarsonous acid is independent of Keap1-C151: enhanced Keap1–Cul3 interactionToxicology and Applied Pharmacology, 2008
- Nrf2 protects human bladder urothelial cells from arsenite and monomethylarsonous acid toxicityToxicology and Applied Pharmacology, 2007
- INFLUENCE OF DIETARY SELENIUM ON THE DISPOSITION OF ARSENATE IN THE FEMALE B6C3F1, MOUSEJournal of Toxicology and Environmental Health, 1997
- Comutagenesis of sodium arsenite with ultraviolet radiation in Chinese hamster V79 cellsBioMetals, 1991
- Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radicalBiochemical and Biophysical Research Communications, 1990
- Dimethylated arsenics induce DNA strand breaks in lung via the production of active oxygen in miceBiochemical and Biophysical Research Communications, 1989
- Tissue distribution and retention of74As-dimethylarsinic acid in mice and ratsArchives of Environmental Contamination and Toxicology, 1984