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Mutagenesis Advance Access originally published online on March 15, 2007
Mutagenesis 2007 22(4):255-261; doi:10.1093/mutage/gem010
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© The Author 2007. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org.

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

R Colognato1, F Coppedè2, J Ponti3, E Sabbioni3 and L Migliore1,*

1Department of Human and Environmental Sciences, University of Pisa, Via S. Giuseppe 22, 56126 Pisa, Italy 2Department of Neurosciences, University of Pisa, Via Roma 67, 56126 Pisa, Italy 3European Commission, Institute for Health and Consumer Protection, ECVAM Unit, JRC-Ispra, TP 580, Via E. Fermi 1, 21020 Ispra, VA, Italy

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 (DMAsV) 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.

* To whom correspondence should be addressed. Tel: +39050836223; Fax: +39050551290; Email: l.migliore{at}geog.unipi.it

Received on July 4, 2006; revised on January 12, 2007; accepted on January 31, 2007.


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 Hum Exp ToxicolHome page
A. Vahidnia, G.B. van der Voet, and F.A. de Wolff
Arsenic neurotoxicity A review
Human and Experimental Toxicology, October 1, 2007; 26(10): 823 - 832.
[Abstract] [PDF]


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