title: A zinc-resistant human epithelial cell line is impaired in cadmium and manganese import.
abstract: A human epithelial cell line (HZR) growing with high zinc concentrations has been analyzed for its ability to sustain high cadmium concentrations. Exposure to up to 200 microM of cadmium acetate for 24 h hardly impacted viability, whereas most of parental HeLa cells were killed by less than 10 microM of cadmium. Upon challenge by 35 fold higher cadmium concentrations than HeLa cells, HZR cells did not display increased DNA damage, increased protein oxidation, or changed intracellular cadmium localization. Rather, the main cause of resistance against cadmium was by avoiding cadmium entry into cells, which differs from that against zinc as the latter accumulates inside cells. The zinc-resistant phenotype of these cells was shown to also impair extracellular manganese uptake. Manganese and cadmium competed for entry into HeLa cells. Probing formerly identified cadmium or manganese transport systems in different animal cells did not evidence any significant change between HeLa and HZR cells. These results reveal zinc adaptation influences manganese and cadmium cellular traffic and they highlight previously unknown connections among homeostasis of divalent metals.
authors.affiliation: CEA, DSV, IRTSV, Laboratoire de Chimie et Biologie des Métaux, Grenoble, France.
authors.forename: Estelle
authors.initials: E
authors.lastname: Rousselet
authors.forename: Pierre
authors.initials: P
authors.lastname: Richaud
authors.forename: Thierry
authors.initials: T
authors.lastname: Douki
authors.forename: Jocelyne Garcia
authors.initials: JG
authors.lastname: Chantegrel
authors.forename: Alain
authors.initials: A
authors.lastname: Favier
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bouron
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Moulis
mesh_terms: D001692:Biological Transport; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D004351:Drug Resistance; D004847:Epithelial Cells / Q000187:drug effects; D005978:Glutathione / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008345:Manganese / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002104:Cadmium; D008345:Manganese; D005978:Glutathione; D015032:Zinc