Sensitivity of hamster tracheal epithelial cells to asbestiform minerals modulated by serum and by transforming growth factor beta 1.

A number of proliferative and cytotoxic responses similar to those induced by classical tumor promoters such as 12-O-tetradecanoylphorbol-13-acetate occur in tracheal epithelial cells and organ cultures exposed to asbestiform minerals. In these studies, cloned diploid hamster tracheal epithelial cells were examined in a number of short term (3-24 h) and long term (greater than 24 h) biological assays for their responsiveness to crocidolite asbestos in comparison to other fibers (chrysotile asbestos, Code 100 fiberglass) and particulates (riebeckite, antigorite, glass beads). In addition, the influence of serum on the biological effects of crocidolite were assessed. In 10% serum-containing medium, low concentrations of crocidolite (1.0 micrograms/cm2 dish) stimulated cellular proliferation (measured as increased [3H]thymidine incorporation), and concentrations greater than 5 micrograms/cm2 dish were cytotoxic (measured by decreased colony forming efficiency). In 2% serum-containing medium, lower concentrations of fibers (0.1-0.5 micrograms/cm2 dish) caused increases in [3H]thymidine incorporation and colony forming efficiency whereas higher concentrations of fibers were required for responses equitoxic to those observed in 10% serum. Crocidolite-induced [3H]thymidine incorporation was inhibited when 2% serum-containing medium was supplemented with transforming growth factor type beta at concentrations (3 ng/ml) which give rise to altered morphology of hamster tracheal epithelial cells. Furthermore, the profiles of colony forming efficiency and 51Cr release of cells grown in the presence of transforming growth factor beta resembled those of cells grown in 10% serum. Results suggest that the phenotypic changes induced by serum factors such as transforming growth factor beta influence the sensitivity of hamster tracheal epithelial cells to crocidolite asbestos.