Genotoxicity induced by arsenic compounds in peripheral human lymphocytes analysed by cytokinesis-block micronucleus assay

Abstract

This work focuses on the analysis of genotoxic effects on human peripheral lymphocytes exposed in vitro to different arsenic (As) compounds by means of the cytokinesis-block micronucleus assay. The study was carried out by challenging peripheral human lymphocytes with six As compounds in trivalent or pentavalent forms such as arsenite (AsIII) and arsenate (AsV) and organoarsenic species such as monomethylarsonous acid (MMAsIII), monomethylarsonic acid (MMAsV), dimethylarsinic acid (DMAs V) and trymethylarsine oxide (TMAOV). For AsIII and AsV at concentrations of 4 and 32 μM, respectively, an increase of micronuclei (MN) frequency was found. MMAsIII and MMAsV induced a statistically significant increase of MN frequency at the dose of 2 and 500 μM, respectively. For DMAsV, no significant increase of MN was observed, although a decrease of the nuclear division index (NDI) was evident, indicating a cytotoxic effect. The genotoxic mechanism of action of MMAsIII was further evaluated by means of fluorescence in situ hybridization analysis. Due to a higher percentage of centromere-positive MN, MMAsIII showed a clear aneuploidogenic property. Finally, for TMAOV no genotoxicity was observed up to 1 mM. These results show how speciation is important in determining the genotoxic and cytotoxic effects of As compounds in human peripheral lymphocytes and support the emerging hypothesis that the induction of aneuploidy could be a mechanism by which As exerts its carcinogenic properties. © The Author 2007. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved.