As2O3-induced oxidative stress and cycle progression in a human intestinal epithelial cell line (Caco-2).
Foods and drinking water are the main routes for human exposure to inorganic arsenic, the intestinal epithelium being the first barrier against such exogenous toxicants. The present study evaluates the effect of As(III) (0.5-25 microM) upon Caco-2 cells as an intestinal epithelia model. Cell viability, intracellular formation of reactive oxygen species (ROS), mitochondrial membrane potential (Deltapsim) changes, and cell cycle distribution in exposed cultures were evaluated. The intracellular production of ROS was seen to increase in a non-dose dependent manner at all concentrations tested, with impairment of cell mitochondrial enzyme function secondary to a loss of Deltapsim. Concentrations between 0.5 and 5 microM induce cell cycle transition from phase G1 to phase S, with no significant alteration in the proportion of cells in phase G2. These data suggest that As(III) could induce intestinal oxidative stress-cytotoxicity at mitochondrial functional level, and affect cell cycle progression. The data presented in this work may also suggest the impairment of essential survival processes in Caco-2 cells, induced after exposure to As(III) (1-25 microM). Oxidative stress and alteration of mitochondrial functionality could be early indicators of arsenic-induced cytotoxicity, with the resulting abnormal progression of the cell cycle.
Laparra
J M
JM
Instituto de Agroquímica y Tecnología de Alimentos-CSIC, Apdo. 73, 46100 Burjassot, Valencia, Spain. mlaparra@iata.csic.es
Vélez
D
D
Barberá
R
R
Farré
R
R
Montoro
R
R
D000077237:Arsenic Trioxide; D001152:Arsenicals; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles
D001152:Arsenicals; D010087:Oxides; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D000077237:Arsenic Trioxide