Toxicological characterization of the inorganic and organic arsenic metabolite Thio- DMA V in cultured human lung cells

We synthesised and toxicologically characterised the arsenic metabolite thiodimethylarsinic acid (thio- dma v). successful synthesis of highly pure thio- dma v was confirmed by state-of-the-art analytical techniques including h 1 -nmr,hplc-ftms,and hplc-icpms. toxicological characterization was carried out in comparison to arsenite and its well-known trivalent and pentavalent methylated metabolites. it comprised cellular bioavailability as well as different cytotoxicity and genotoxicity end points in cultured human a549 lung cells. of all arsenicals investigated,thio- dma v exerted the strongest cytotoxicity. moreover,thio- dma v did not induce dna strand breaks and an increased induction of both micronuclei and multinucleated cells occurred only at beginning cytotoxic concentrations,indicating that thio- dma v does not act via a genotoxic mode of action. finally,to assess potential implications of thio- dma v for human health,further mechanistic studies are urgently necessary to identify the toxic mode of action of this highly toxic,unusual pentavalent organic arsenical. copyright © 2011 marc bartel et al.