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 chal- 15 lenging 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 20 trymethylarsine oxide (TMAOV). For AsIII and AsV at concentrations of 4 and 32 mM, 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 mM, respectively. For 25 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 30 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 35 human peripheral lymphocytes and support the emerging hypothesis that the induction of aneuploidy could be a mechanism by which As exerts its carcinogenic properties
Genotoxicity induced by arsenic compounds in peripheral human lymphocytes analysed by cytokinesis-block micronucleus assay
COPPEDE', FABIO;MIGLIORE, LUCIA
2007-01-01
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 chal- 15 lenging 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 20 trymethylarsine oxide (TMAOV). For AsIII and AsV at concentrations of 4 and 32 mM, 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 mM, respectively. For 25 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 30 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 35 human peripheral lymphocytes and support the emerging hypothesis that the induction of aneuploidy could be a mechanism by which As exerts its carcinogenic propertiesI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
