These experiments have shown that human mesothelial cells, as compared to fibroblasts, are more sensitive to induction of structural chromosomal aberrations by exposure to asbestos fibers. In addition, it has been shown that malignant mesothelioma cell lines produce PDGF A-chain and B-chain mRNA at much higher levels than do normal cells. PDGF-like activity is detected in medium conditioned by tumor cells, but not by normal cells. TGF-beta mRNA is expressed at similar levels in normal cells and tumor cells, but TGF-beta protein is secreted in greater amounts by normal cells. Normal cells respond to mitogenic stimuli from PDGF and possess PDGF receptors. These findings suggest the possibility of an autocrine mechanism for the generation of mesothelioma. Two-dimensional gel analysis of normal human bronchial epithelial cells after TPA or TGF-beta treatment has indicated several protein alterations which might correlate with squamous differentiation. The magnitude of the alterations is not great, implying that this technique may not display the most critical changes. It is of interest that Northern blot analysis indicates that a 2-hour treatment of human bronchial epithelial cells with TPA, but not TGF-beta, can induce an increase in IL-1 beta.
