Journal
ARCHIVES OF TOXICOLOGY
Volume 94, Issue 8, Pages 2587-2601Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00204-020-02772-9
Keywords
Arsenic; Metalloid; Methylation; Reduction; Arsine; Glutathione; Promyelocytic leukemia
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Funding
- Japan Society for the Promotion of Science [16K15386]
- Grants-in-Aid for Scientific Research [16K15386] Funding Source: KAKEN
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Arsenic is a well-known environmental carcinogen and chronic exposure to arsenic through drinking water has been reported to cause skin, bladder and lung cancers, with arsenic metabolites being implicated in the pathogenesis. In contrast, arsenic trioxide (As2O3) is an effective therapeutic agent for the treatment of acute promyelocytic leukemia, in which the binding of arsenite (iAs(III)) to promyelocytic leukemia (PML) protein is the proposed initial step. These findings on the two-edged sword characteristics of arsenic suggest that after entry into cells, arsenic reaches the nucleus and triggers various nuclear events. Arsenic is reduced, conjugated with glutathione, and methylated in the cytosol. These biotransformations, including the production of reactive metabolic intermediates, appear to determine the intracellular dynamics, target organs, and biological functions of arsenic.
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