Title: In vitro DNA damage by arsenic compounds in a human lymphoblastoid cell line (TK6) assessed by alkaline Comet assay
Citation: MUTAGENESIS vol. 19 no. 2 p. 129-135
Publication Year: 2004
JRC N°: JRC36847
ISSN: 0267-8357
URI: http://mutage.oxfordjournals.org/content/19/2/129
DOI: 10.1093/mutage/geh005
Type: Articles in periodicals and books
Abstract: This work focuses on the analysis of genotoxic effects on human peripheral lymphocytes exposed in vitro to arsenic compounds by means of the cytokinesis-block micronucleus assay (CBMN). The study was carried out on three non-smoker healthy males challenged with six arsenic compounds, in trivalent or pentavalent formsuch as sodium arsenite (NaAsO2) and sodium arsenate (NaHAsO4*7H2O) and organoarsenic species such as monomethylarsonous acid (MMAsIII), monomethylarsonic acid (MMAsV), dimethylarsonous acid (DMAsV) and trimethyl arsine oxide (CH3)3AsO (TMAO). For AsIII and AsV at the concentration of 4 M and 32 M 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 M respectively. For DMAsV no significant increase of MN was observed, although a decrease of the cytokinesis block proliferation index (CBPI) was evident, indicating a cytotoxic effect. Since the knowledge on the genotoxic effects of the trivalent monomethylated compound is rare or even missing we decided also to evaluate the genotoxic mechanism of action of MMAIII by means of FISH analysis. Due to higher percentage of centromeres positive MN, MMAIII showed a clear aneuploidogenic properties. Finally for TMAO no toxicity was observed up to 1 mM. These results show how speciation is a key factor in determining the cytotoxic effects of As compounds in human peripheral lymphocytes bringing into highlight the need to better understand the molecular mechanisms involved in arsenic poisoning.
JRC Directorate:Institute for Health and Consumer Protection Historical Collection

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