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THE CELLULAR METABOLISM AND SYSTEMIC TOXICITY OF ARSENIC
Citation:
Thomas, D J., M. Styblo, AND S. Lin. THE CELLULAR METABOLISM AND SYSTEMIC TOXICITY OF ARSENIC. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press, New York, NY, 176:127-144, (2001).
Description:
Abstract
Toxic Consequences of the Metabolism of Arsenic. David J. Thomas, Miroslav Styblo, and Shan Lin. (2001). Toxicol. Appl. Pharmacol. 000, xxx-yyy.
Although it has been known for decades that humans and many other species metabolize inorganic arsenic to methyl arsenic and dimethyl arsenic, little attention has been given to the biological effects of these methylated products. It was widely held that inorganic arsenic was the species that accounted for the toxic and carcinogenic effects of this metalloid and that methylation was properly regarded as a mechanism for detoxification of arsenic. Elucidation of the metabolic pathway for arsenic has changed our understanding of the significance of methylation. Both methyl arsenic and dimethyl arsenic that contain arsenic in the trivalent oxidation state have been identified as intermediates in the metabolic pathway. These compounds have been detected in human cells cultured in the presence of inorganic arsenic and in urine of individuals chronically exposed to inorganic arsenic. Methyl arsenic and dimethyl arsenic that contain arsenic in the trivalent oxidation state are more cytotoxic, more genotoxic, and more potent inhibitors of the activities of some enzymes than is inorganic arsenic containing arsenic in the trivalent oxidation state. Hence, it is reasonable to describe the methylation of arsenic as a pathway for its activation, not as a mode of detoxification. This review summarizes the current knowledge of the processes that control the formation and fate of the methylated metabolites of arsenic and of the biological effects of methyl and dimethyl arsenic. Given the considerable interest in the dose-response relationships for arsenic as a toxin and a carcinogen, understanding the metabolism of arsenic may be critical to assessing the risk associated with chronic exposure to this element.
Key Words - arsenic, inorganic arsenic, methyl arsenic, dimethyl arsenic, metabolism, human, rat, mouse