Mechanisms of cytotoxicity of asbestos fibres in rat tracheal epithelial cells in culture

Abstract

Little is known about the mechanism(s) of asbestos toxicity, especially in respiratory epithelium. Studies were carried out to elucidate some important aspects of the cytotoxic effects of asbestos, using a tracheal epithelial cell line in culture. Chrysotile and crocidolite asbestos with similar aspect ratios were used. Both induced in 2C5 cells a concentration-dependent inhibition of colony-forming ability, a measure of proliferative capacity. In this respect, chrysotile (LC 50, 0.95 μg/cm 2) was about six times more toxic than crocidolite (LC 50, 5.8 μg/cm 2). Both types of asbestos caused only minor changes in membrane permeability, measured by trypan blue exclusion and by [ 75Se]selenomethionine release, even at concentrations of asbestos that caused > 90% inhibition in colony formation. Thus membrane damage was only a minor component of the toxicity produced by the fibres. Chrysotile was phagocytized much more readily than crocidolite and produced an approximately threefold greater increase in binucleated cells and micronuclei than crocidolite, suggesting that phagocytosis was the rate-limiting step in fibre toxicity. Our studies suggest a potentially important pathway of fibre toxicity involving binding, phagocytosis, nuclear damage, disruption of mitosis, inhibition of proliferation and/or cell death. In this process, the fibre aspect ratio is not the only determinant of fibre toxicity, since chrysotile and crocidolite fibres of similar length and diameter exhibit very different degrees of toxicity. It appears that other fibre characteristics, such as fibre surface charge, are of equal importance.