Cultured Human Mesothelial Cells are Selectively Sensitive to Cell Killing by Asbestos and Related Fibers: A Potential in Vitro Assay for Carcinogenicity

Abstract

The use of man-made fibers as substitutes for asbestos is increasing, and it is important to determine the potential health hazards, including potential carcinogenicity, of these fibers. It is of particular interest to develop short-term in vitro assays that could significantly decrease the need for animal testing as well as provide rapid and reliable information to industry during the time that applications for new fibers are being developed. One potential rapid screening assay for mesothelioma-causing fibers is selective cytotoxicity for cultured human mesothelial cells. Cell killing of cultured normal human mesothelial cells by amosite, chrysotile, or crocidolite fibers occurs at levels of exposure approximately 50 fold less those required to produce cell killing cultured human lung fibroblasts. This differential cytotoxic effect is also observed for erionite, a fibrous zeolite linked to mesothelioma in Turkey, and Code 100 glass fiber found to cause mesothelioma in laboratory animals. In contrast, both mesothelial cells and fibroblasts require similar high levels of exposure to fibers such as Wollastonite, glass wool, and refractory ceramic fibers for cell killing. Non-fibrous particulates such as aluminum oxide, and a variety of chemicals are also toxic for both cell types at similar concentrations. Thus, human mesothelial cells, a selective in vivo target to the carcinogenic effects of asbestiform fibers, are also a selective in vitro target of the cytotoxic effects of these fibers. Differential cytotoxicity for cultured mesothelial cells and fibroblasts may be useful for predicting the potential of new man-made fibers to cause mesothelioma.