Differential toxicity and gene expression in Caco-2 cells exposed to arsenic species.
Inorganic arsenic [As(V)+As(III)] and its metabolites, especially the trivalent forms [monomethylarsonous acid, MMA(III), and dimethylarsinous acid, DMA(III)], are considered the forms of arsenic with the highest degree of toxicity, linked to certain types of cancer and other pathologies. The gastrointestinal mucosa is exposed to these forms of arsenic, but it is not known what toxic effect these species may have on it. The aim of the present work was to evaluate the toxicity and some mechanisms of action of inorganic arsenic and its metabolites [monomethylarsonic acid, MMA(V), dimethylarsinic acid, DMA(V), MMA(III) and DMA(III)] in intestinal epithelial cells, using the Caco-2 human cell line as a model. The results show that the pentavalent forms do not produce toxic effects on the intestinal monolayer, but the trivalent species have a different degree of toxicity. As(III) induces death mainly by necrosis, whereas only apoptotic cells are detected after exposure to MMA(III), and for DMA(III) the percentages of apoptosis and necrosis are similar. The three forms produce reactive oxygen species, accompanied by a reduction in intracellular GSH and lipid peroxidation, the latter being especially notable in the dimethylated form. They also alter the enzyme activity of glutathione peroxidase and catalase and induce expression of stress proteins and metallothioneins. The results indicate that the trivalent forms of arsenic can affect cell viability of intestinal cells by mechanisms related to the induction of oxidative stress. Further studies are needed to evaluate how the effects observed in this study affect the structure and functionality of the intestinal epithelium.
Instituto de Agroquímica y Tecnología de Alimentos (IATA-CSIC), Avenida Agustín Escardino n° 7, 46980 Paterna, Valencia, Spain.
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D017209:Apoptosis / Q000187:drug effects; D001152:Arsenicals / Q000009:adverse effects*; D018938:Caco-2 Cells; D002101:Cacodylic Acid / Q000633:toxicity*; D002274:Carcinogens, Environmental / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006540:Herbicides / Q000633:toxicity*; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects; D009336:Necrosis / Q000139:chemically induced; D018384:Oxidative Stress / Q000187:drug effects; D010088:Oxidoreductases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D001152:Arsenicals; D002274:Carcinogens, Environmental; D006360:Heat-Shock Proteins; D006540:Herbicides; D017382:Reactive Oxygen Species; D008668:Metallothionein; D002101:Cacodylic Acid; D010088:Oxidoreductases; D005978:Glutathione; C020300:monomethylarsonic acid