Pattern of stress protein expression in human lung cell-line A549 after short- or long-term exposure to cadmium

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 str ess protein, which indicates repair of damaged proteins, could be a sensiti ve and early biomarker of environmental pollution by Cd. In comparative stu dies, we examined the effects of exposure to Cd (as CdCl2) on the growth ra te of the A549 pulmonary cell line, and (by Western blot analyses) on the i nduction of the hsp72 stress protein and metallothioneins (MTs). CdCl2 expo sure was studied for periods of 2 hr to 1 month. For short-term exposure (2 -6 hr) to Cd concentrations higher than 50 mu M, an overexpression of hsp72 appeared 6 hr later, suggesting that hsp72 might be considered an early bi omarker of acute exposure to Cd. For exposures lasting more than 4 days, lo wer doses of Cd (0.1-10 mu M) similar to levels encountered in occupational exposure induced a significant increase of the hsp72 level. Because the in crease of hsp72 occurs for doses that did not affect cell proliferation, ou r work supports the idea that its overexpression might be used as a sensiti ve indicator of occupational exposure to Cd. However, increased resistance to Cd appeared in A549 cells exposed for 1 month and overexpression of hsp7 2 disappeared simultaneously. It is possible that, ill vivo, cell adaptatio n also occurs throughout chronic exposure to Cd, with a decrease of hsp ind uction as a consequence. A dose-related increase of MTs was found after 4 d ays of exposure to Cd concentrations ranging from 0.1 to 10 mu M without ch ange of overexpression during chronic exposure, suggesting that MT expressi on could be a more constant indicator of Cd pollution. Because 0.1 mu M Cd (11 mu g/L) induces hsp72 expression, showing the presence of damaged prote ins, our work suggests that the maximum allowable biologic exposure limit s hould be lowered.