Effects of heavy metals on structure, function, and metabolism of ciliated respiratory epithelium in vitro

Tracheal explants were used to evaluate the relative ciliostatic and cytotoxic potential of heavy metal salts (cadmium chloride, chromium chloride, nickel chloride, and copper sulfate). Explants from hamster, rat, and guinea pig were all sensitive to the metals, though guinea pig explants showed the greatest difference between the untreated and metal treated tissues. Dosage levels were 50, 100, and 500 microM, for 24 to 148 h. Cadmium caused the greatest degree of ciliostasis and cell necrosis. Copper was less toxic, and nickel and chromium caused marginal damage when tested at 100 microM or lower. In each instance, damage became detectable at approximately 24 to 48 h and was nearly stabilized by 72 h. A significant loss of ciliary motion was always accompanied by a decrease in metabolic activity (dehydrogenase activity and ATP content). Transmission and scanning electron microscopy revealed a severely necrotic epithelium after exposure to cadmium, with only subtle morphological alterations after exposure to other metals. With all of the treatments there was no overt structural damage to cilia and little alteration in membranes of cells remaining in the epithelium. Some coagulation or vacuolization was noted in cadmium and copper treated explants but most cellular organelles did not display obvious damage. The most significant changes in the tracheal epithelium exposed to heavy metal salts in vitro were a loss of ciliary motion and a decrease in total ATP content.