Biotransformation of arsenic and toxicological implication of arsenic metabolites

Arch Toxicol. 2020 Aug;94(8):2587-2601. doi: 10.1007/s00204-020-02772-9. Epub 2020 May 20.

Abstract

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 (iAsIII) 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.

Keywords: Arsenic; Arsine; Glutathione; Metalloid; Methylation; Promyelocytic leukemia; Reduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Arsenic Poisoning / etiology*
  • Arsenic Poisoning / metabolism
  • Arsenic Trioxide / metabolism
  • Arsenic Trioxide / pharmacology*
  • Arsenicals / metabolism
  • Arsenicals / pharmacology*
  • Biotransformation
  • Humans
  • Leukemia, Promyelocytic, Acute / drug therapy*
  • Leukemia, Promyelocytic, Acute / metabolism
  • Leukemia, Promyelocytic, Acute / pathology
  • Risk Assessment
  • Toxicity Tests

Substances

  • Antineoplastic Agents
  • Arsenicals
  • Arsenic Trioxide