Transition Metal Mediated Free Radical Formation In Vitr

Environmental Health Sciences

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Abstract

Acute toxicity of arsenic is dependent on its chemical forms and the proximity to high local arsenic concentrations is one of the mechanisms for cell death. The study was designed to define acute arsenic-induced stress-related gene expression in vivo in mice. The Atlas mouse stress/toxicology array revealed that the expression of genes related to stress, DNA damage, and metabolism was altered by arsenic treatments. Thus the expression of heme-oxygenase was increased 10-fold along with increases in heat-shock protein-60(HSP60), DNA damage inducible GADD45 , and the DNA excision repair protein ERCC1. Western blot analysis further confirmed the enhanced production of arsenic-induced stress proteins such as HO-1, HSP70, HSP90, metallothionein, the metal-responsive transcription factor MTF-1, nuclear factor kappa B and c-jun/AP-1. Increases in caspase 1 and cytokines such as TNF-alfa and macrofage inflammatory protein-2 were also evident. Under these experimental conditions no free radical metabolites were detected by ESR. In summary, the study profiled the gene expression pattern in mice treated with inorganic arsenicals, which adds to our understanding of the molecular mechanism of acute arsenic poisoning and toxicity.