title: A metal mixture induces transformation upon antioxidant depletion in a hepatic cell line.
abstract: BACKGROUND
  Metals are ubiquitous soil, air, and water pollutants. A mixture of arsenic cadmium and lead, in particular, has commonly been found in the vicinity of smelter areas. The mixture of As-Cd-Pb has been shown to be carcinogenic, and transforming potential and oxidative stress have been proposed as principal mechanisms involved in this process. The aim of this work was to explore the role of the antioxidant barrier in the establishment of cell transformation upon chronic exposure to a metal mixture containing 2 μM NaAsO(2), 2 μM. CdCl(2), and 5 μM Pb(C(2)H(3)O(2))(2)∙3H(2)O in WRL-68 cells-a non-transformed human hepatic cell line.
  
  
  METHODS
  In this study, we used a WRL-68 cell model of human embryonic hepatic origin treated with antioxidant inhibitors (L-Buthionine-sulfoxamine and aminotriazole) to test the role of the antioxidant barrier in the establishment of cell transformation upon chronic exposure to a metal mixture of As-Cd-Pb (2 μM NaAsO(2), 2 μM CdCl(2) and 5 μM Pb(C(2)H(3)O(2))(2)∙3H(2)O). We evaluated oxidative damage markers, including reactive oxygen species, lipid peroxidation, and genotoxicity, as well as antioxidant response markers, including glutathione concentration, catalase activity, and superoxide dismutase activity, which promote morphological transformation, which can be quantified by foci formation.
  
  
  RESULTS
  As expected, we found an increase in the intracellular concentration of the metals after treatment with the metal mixture. In addition, treatment with the metal mixture in addition to inhibitors resulted in a large increase in the intracellular concentration of cadmium and lead. Our results describe the generation of reactive oxygen species, cytotoxicity, genotoxicity, and oxidative damage to macromolecules that occurred exclusively in cells that were morphologically transformed upon exposure to a metal mixture and antioxidant barrier inhibition.
  
  
  CONCLUSIONS
  Our results show the importance of the antioxidant barrier role in the protection of cellular integrity and the transformation potential of this metal mixture via free radicals.
authors: Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México.
authors: Vicente
authors: V
authors: Sánchez-Valle
authors: Mahara
authors: M
authors: Valverde
authors: Leticia
authors: L
authors: Carrizale
authors: Jesus
authors: J
authors: Mejía
authors: Nahum
authors: N
authors: Zepeta
authors: Emilio
authors: E
authors: Rojas
mesh_terms: D000640:Amitrole / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism / Q000633:toxicity*; D019328:Buthionine Sulfoximine / Q000633:toxicity; D019256:Cadmium Chloride / Q000378:metabolism / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009942:Organometallic Compounds / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017670:Sodium Compounds / Q000378:metabolism / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D000975:Antioxidants; D018053:Arsenites; D009942:Organometallic Compounds; D017382:Reactive Oxygen Species; D017670:Sodium Compounds; C017947:sodium arsenite; D019328:Buthionine Sulfoximine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D019256:Cadmium Chloride; C008261:lead acetate; D000640:Amitrole