Selected mechanisms of genotoxic effects of inorganic arsenic compounds.

Chronic exposure to inorganic arsenic compounds is responsible for the prevalance of various tumors, as well as of other diseases. A major problem is the exposure to inorganic arsenic (i-As) in drinking water that affects millions of people, primarily in Asia and South America. In these regions, the concentration of arsenic in drinking water amounts to several thousand microg/l and considerably exceeds the standard of 50 microg/l, recommended by the US Environmental Protection Agency. It is interesting that not all populations are equally sensitive to i-As. Therefore, the existing standard should be verified and the environmentally safe i-As concentration should be established. Bearing this in mind, it would be helpful to know the mechanisms of toxicity of inorganic arsenic compounds. In vitro and in vivo studies and examination of people exposed to high concentrations of i-As in drinking water show its genotoxicity. Inorganic As increases the frequency of micronuclei, chromosome aberrations and sister chromatid exchanges both in humans and in animals, but it does not induce point mutations. If arsenic does not affect DNA directly, then what is the mechanism of its toxicity? The results of various studies suggest that it may intensify toxic effects of other physical and chemical agents, especially by DNA repair inhibition. Besides, it is believed that inorganic arsenic compounds may cause changes in the cell redox potential and alter DNA methylation and phosphorylation of cell-cycle control proteins. Some data also suggest that i-As increases celluar proliferation and apoptosis. The purpose of this work is to present some views on cytotoxic mechanisms of inorganic arsenic compounds.