Induction of chromosomal aberrations in cultured human fibroblasts by inorganic and organic arsenic compounds and the different roles of glutathione in such induction.
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-beta-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 x 10(-3) M. Arsenosugar, arsenocholine, arsenobetaine and tetramethylarsonium 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.
Oya-Ohta
Y
Y
Department of Pathology, Kanagawa Prefectural College of Nursing and Medical Technology, Yokohama, Japan.
Kaise
T
T
Ochi
T
T
D001152:Arsenicals / Q000494:pharmacology*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D016296:Mutagenesis / Q000187:drug effects*; D013439:Sulfhydryl Reagents / Q000494:pharmacology*
D001152:Arsenicals; D013439:Sulfhydryl Reagents; D019328:Buthionine Sulfoximine; D005978:Glutathione