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METHYLATED TRIVALENT ARSENIC SPECIES ARE GENOTOXIC
Citation:
Mass, M J., A H. Tennant, B C. Roop, W. R. Cullen, M Styblo, D J. Thomas, AND A D. Kligerman. METHYLATED TRIVALENT ARSENIC SPECIES ARE GENOTOXIC. CHEMICAL RESEARCH IN TOXICOLOGY 14(4):355-361, (2001).
Description:
ABSTRACT
The genotoxic effects of arsenic compounds are generally believed to result from other than direct interacton with DNA. The reactivties of methyloxarsine (MAsIII) and iododimethylarsine (DMAsIII), two methylated trivalent arsenicals, toward supercoiled X174 RFI DNA was assessed during a DNA nicking assay. The induction of DNA damage by these compounds in human peripheral lymphocytes in primary culture was assessed in a single cell gel (SCG, comet) assay. Both methylated trivalent arsenicals were able to nick and/or completely degrade X174 DNA in vitro in 2 h incubations at 37 C (pH 7.4) depending on concentration. MAsIII was effective at nicking X174 DNA at 30 mM; however, at 50 MD MAsIII nicking could be observed. Exposure of X174 DNA to sodium arsenite (iAsIII; < 300 mM), sodium arsenate (< 1M), and the pentavalent arsenicals, monomethylarsonic acid (< 3 M) and dimethylarsinic acid (< 300 mM), did not nick or degrade X174 DNA under these conditions. In the SCG assay in human lymphocytes, methylated trivalent arsenicals were much more potent that any other arsenicals tested. Based upon the slopes of the concentration- response curve for tail moment in the SCG assay, MAsIII and DMAsIII were 77 and 433 times more potent than iAsIII, respectively. Because methylated trivalent arsenicals were the only arsenic compounds that were observed to damage naked DNA and required no exogenously added enzymatic or chemical activation systems, we propose that methylated trivalent arsenic species are candidates for the proximate or ultimate genotoxic forms of arsenic.