title: Different mechanisms for metal-induced adaptation to cadmium in the human lung cell lines A549 and H441.
abstract: Sensitivity to Cd and Zn as well as the capacity to develop tolerance were characterized in human lung cells A549 and H441. In the A549 cells, a 2-fold lower LC(50) was obtained for Cd compared to Zn, whereas H441 cells were similarly sensitive to both metals. H441 cells were twice as resistant to Cd as the A549 cells. Higher HSP70, but not metallothionein (MT) or glutathione (GSH) levels, could contribute to this better resistance. A 1.5- and 2-fold increase in the LC(50) for Cd was obtained in the A549 cells pre-exposed to non-cytotoxic concentrations of Cd (20 μM) or Zn (40 μM) for 24 h. On the other hand, only Zn increased H441 cells' resistance to Cd. Maximum Zn- and Cd-induced tolerances were reached as early as 3 and 12 h, respectively. Increases in MT-IIa and HSP70 messenger RNA levels were higher in A549 cells, but cycloheximide eliminated the induction of tolerance only in the H441 cells. Protein synthesis is a prerequisite for metal-induced tolerance to Cd in the H441 cells but not the A549 cells. Results obtained with L-buthionine sulfoximine revealed that GSH synthesis is not responsible for the acquired tolerance in both cell lines. However, GSH plays a critical role against Cd toxicity, and pro-oxidant conditions sensitized cells to Cd with different impacts on the metal-induced mechanisms of acquired tolerance. GSH and catalase both provide antioxidative protection, but only the stress related to low GSH content, not that resulting from catalase inhibition, may be alleviated with Zn.
authors.affiliation: Département des sciences biologiques, Centre TOXEN, Université du Québec à Montréal, C.P. 8888 Succursale Centre-ville, Montréal, QC, Canada, H3C 3P8.
authors.forename: Josée-Anne
authors.initials: JA
authors.lastname: Sauvageau
authors.forename: Catherine
authors.initials: C
authors.lastname: Jumarie
mesh_terms: D000220:Adaptation, Biological; D002104:Cadmium / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D004361:Drug Tolerance; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress; D014176:Protein Biosynthesis; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction; D015032:Zinc / Q000494:pharmacology*
chemical_list: D002413:Cations, Divalent; D018840:HSP70 Heat-Shock Proteins; C491053:MT2A protein, human; D002104:Cadmium; D008668:Metallothionein; D002374:Catalase; D005978:Glutathione; D015032:Zinc