title: Pattern of stress protein expression in human lung cell-line A549 after short- or long-term exposure to cadmium.
abstract: Exposure to cadmium is associated with the development of pulmonary damage such as emphysema and lung cancer. This metal is also a powerful inducer of stress proteins in many biologic models. The present study was undertaken to evaluate whether an overexpression of the heat shock protein (hsp)72 stress protein, which indicates repair of damaged proteins, could be a sensitive and early biomarker of environmental pollution by Cd. In comparative studies, we examined the effects of exposure to Cd (as CdCl(2)) on the growth rate of the A549 pulmonary cell line, and (by Western blot analyses) on the induction of the hsp72 stress protein and metallothioneins (MTs). CdCl(2) exposure was studied for periods of 2 hr to 1 month. For short-term exposure (2-6 hr) to Cd concentrations higher than 50 microM, an overexpression of hsp72 appeared 6 hr later, suggesting that hsp72 might be considered an early biomarker of acute exposure to Cd. For exposures lasting more than 4 days, lower doses of Cd (0.1-10 microM) similar to levels encountered in occupational exposure induced a significant increase of the hsp72 level. Because the increase of hsp72 occurs for doses that did not affect cell proliferation, our work supports the idea that its overexpression might be used as a sensitive indicator of occupational exposure to Cd. However, increased resistance to Cd appeared in A549 cells exposed for 1 month and overexpression of hsp72 disappeared simultaneously. It is possible that, in vivo, cell adaptation also occurs throughout chronic exposure to Cd, with a decrease of hsp induction as a consequence. A dose-related increase of MTs was found after 4 days of exposure to Cd concentrations ranging from 0.1 to 10 microM without change of overexpression during chronic exposure, suggesting that MT expression could be a more constant indicator of Cd pollution. Because 0.1 microM Cd (11 microg/L) induces hsp72 expression, showing the presence of damaged proteins, our work suggests that the maximum allowable biologic exposure limit should be lowered.
authors.affiliation: Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine-Purpan, Toulouse, France.
authors.forename: F
authors.initials: F
authors.lastname: Croute
authors.forename: B
authors.initials: B
authors.lastname: Beau
authors.forename: C
authors.initials: C
authors.lastname: Arrabit
authors.forename: Y
authors.initials: Y
authors.lastname: Gaubin
authors.forename: F
authors.initials: F
authors.lastname: Delmas
authors.forename: J C
authors.initials: JC
authors.lastname: Murat
authors.forename: J P
authors.initials: JP
authors.lastname: Soleilhavoup
mesh_terms: D015415:Biomarkers; D015153:Blotting, Western; D002104:Cadmium / Q000009:adverse effects*; D002455:Cell Division; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors
chemical_list: D015415:Biomarkers; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D002104:Cadmium