title: Induction by arsenate of cell-type-specific cytotoxic effects in nerve and hepatoma cells.
abstract: The aim of the study was to compare the effect of sodium arsenate (AsV) on two different cell types: 158N murine oligodendrocytes and HepG2 human hepatoma cells. Exposure of 158N cells to AsV (0.1-400 µM; 48 h) induced a biphasic cytoxic effect defined as hormesis. Thus, low concentrations of AsV stimulate cell proliferation, as shown by phase-contrast microscopy, cell counting with trypan blue, and crystal violet assay, whereas high concentrations induce cell death associated with a loss of cell adhesion. These side effects were confirmed by staining with propidium iodide and cell cycle analysis, characterized by the presence of a subG1 peak, a criterion of apoptosis. The effects of AsV on mitochondrial function, as determined by the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, the measurement of mitochondrial transmembrane potential with 3,3'-dihexyloxacarbocyanine iodide, and the rate of mitochondrial adenosine triphosphate confirm the impact of AsV on the mitochondria. In contrast to 158N cells, HepG2 cells were susceptible to all AsV concentrations as shown by microscopic observations, by counting with trypan blue. However, no alteration is noted in the cell membrane integrity, which indicated an apoptotic mode of cell death, and this side effect is confirmed by the cycle analysis, which revealed a subG1 peak. Of note, there was a loss of MTT, suggesting that AsV induces mitochondrial complex II dysfunction. Altogether, our data show that the cytotoxic characteristics of AsV depend on the cell type considered.
authors.affiliation: 1 Laboratory Bio-PeroxIL, Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA7270/INSERM, Faculty of Sciences Gabriel, University of Bourgogne Franche Comté, Dijon, France.|2 Laboratory of Nutrition-Functional Foods and Vascular Diseases, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Wafa
authors.initials: W
authors.lastname: Kharroubi
authors.affiliation: 1 Laboratory Bio-PeroxIL, Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA7270/INSERM, Faculty of Sciences Gabriel, University of Bourgogne Franche Comté, Dijon, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nury
authors.affiliation: 1 Laboratory Bio-PeroxIL, Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA7270/INSERM, Faculty of Sciences Gabriel, University of Bourgogne Franche Comté, Dijon, France.|2 Laboratory of Nutrition-Functional Foods and Vascular Diseases, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Samia Haj
authors.initials: SH
authors.lastname: Ahmed
authors.affiliation: 1 Laboratory Bio-PeroxIL, Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA7270/INSERM, Faculty of Sciences Gabriel, University of Bourgogne Franche Comté, Dijon, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Andreoletti
authors.affiliation: 2 Laboratory of Nutrition-Functional Foods and Vascular Diseases, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Rachid
authors.initials: R
authors.lastname: Sakly
authors.affiliation: 2 Laboratory of Nutrition-Functional Foods and Vascular Diseases, Faculty of Medicine, University of Monastir, Monastir, Tunisia.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Hammami
authors.affiliation: 1 Laboratory Bio-PeroxIL, Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism EA7270/INSERM, Faculty of Sciences Gabriel, University of Bourgogne Franche Comté, Dijon, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lizard
mesh_terms: D000818:Animals; D001149:Arsenates / Q000008:administration & dosage / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular; D002453:Cell Cycle; D016923:Cell Death / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015386:Hazardous Substances; D056945:Hep G2 Cells; D059165:Hormesis; D006801:Humans; D008113:Liver Neoplasms; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009836:Oligodendroglia / Q000187:drug effects*
chemical_list: D001149:Arsenates; D015386:Hazardous Substances; C009277:sodium arsenate
keywords: 158N murine oligodendrocytes; HepG2 human hepatoma cells; Sodium arsenate; mitochondria; oxidative phosphorylation; redox homeostasis