| Pattern of Stress Protein Expression in Human Lung Cell-Line A549 after Short- or Long-Term Exposure to Cadmium Françoise Croute, Bernadette Beau, Christine Arrabit, Yolande Gaubin, Florence Delmas, Jean-Claude Murat, and Jean-Pierre Soleilhavoup Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine-Purpan, Toulouse, France 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 CdCl2) 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) . CdCl2 exposure was studied for periods of 2 hr to 1 month. For short-term exposure (2-6 hr) to Cd concentrations higher than 50 µM, 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 µM) 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 µM without change of overexpression during chronic exposure, suggesting that MT expression could be a more constant indicator of Cd pollution. Because 0.1 µM Cd (11 µg/L) induces hsp72 expression, showing the presence of damaged proteins, our work suggests that the maximum allowable biologic exposure limit should be lowered. Key words: cadmium, chronic exposure, heat shock proteins, lung epithelial cells, metallothioneins. Environ Health Perspect 108:55-60 (2000) . [Online 13 December 1999] http://ehpnet1.niehs.nih.gov/docs/2000/108p55-60croute/ abstract.html Address correspondence to F. Croute, Laboratoire de Biologie Cellulaire et Pollution, Faculté de Médecine-Purpan, 37 allées Jules Guesde, 31073 Toulouse, France. Telephone: 33 0561 145 940. Fax: 33 0561 145 945. E-mail: jsoleilh@cict.fr This research was supported by grant 9693036 from the Agence de l'Environnement et de la Maîtrise de l'Energie, France. Received 20 May 1999 ; accepted 4 August 1999.
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