Induction of chromosomal aberrations in cultured human fibroblasts by inorganic and organic arsenic compounds and the different roles of glutathione in such induction

Abstract

Clastogenic effects of a variety of arsenic compounds were examined on cultured human fibroblasts. The following compounds were tested: inorganic arsenicals (arsenite and arsenate), the major metabolites of inorganic arsenicals in human and experimental animals [methylarsonic acid (MAA), dimethylarsinic acid (DMAA) and trimethylarsine oxide (TMAO)], and water-soluble organoarsenic derivatives [2′,3′-dihydroxypropyl-5-deoxy-5-dimethylarsinoyl-β- d-riboside (arsenosugar), arsenocholine, arsenobetaine and tetramethylarsonium iodide] found in marine organisms. Arsenic compounds induced mainly chromatid gaps and chromatid breaks. The rank order of compounds in terms of clastogenic potency was arsenite arsenate DMAA MAA TMAO. DMAA was very potent and caused chromosome pulverizations in most metaphases when present at doses higher than 7 × 10 −3 M. Arsenosugar, arsenocholine, arsenobetaine and tetrametylarsonium iodide were less effective. Depletion of cellular glutathione (GSH) with l-buthionine-SR-sulfoximine (BSO), increased the incidence of chromosomal aberrations induced by arsenite, arsenate and MAA, and markedly suppressed the clastogenic effects of DMAA. DMAA was highly clastogenic even in GSH-depleted cells when the cells were incubated with DMAA in the presence of GSH (5 and 10 mM). These results suggest that GSH might play a role in protecting cells against the clastogenic effects of arsenite, arsenate and MAA. GSH might be involved in the expression of clastogenic actions of DMAA.