Inhibition of asbestos‐induced transformation of rat pleural mesothelial cells in co‐culture with rat macrophages

The aim of this work was to investigate the influence of macrophages on the process of rat pleural mesothelium cells (RPMC) transformation in vitro. For this purpose prolonged many-passage co-cultivation of rat pleural mesothelial cells and rat peritoneal macrophages was performed both in the presence (to study macrophage influence on asbestos-induced morphologic transformation) and in the absence (to study spontaneous transformation) of asbestos. It was shown that spontaneous transformation of RPMC slightly accelerated in the co-cultures, whereas asbestos-induced transformation was strongly inhibited. For instance, RPMC acquired the ability to form multilayer cell growth foci and colonies in semisolid agar at 22-24 passages in the absence and at 14-16 passages in the presence of asbestos, while in co-culture with macrophages these signs of transformation appeared at 17-19 passages without asbestos treatment and were not observed at the 40th passage under exposure to asbestos. It was shown that the observed inhibition of transformation was caused by preferential depletion of transformed cells in co-cultures of mesothelium and macrophages in the presence of asbestos: when equal concentrations of macrophages and asbestos were taken, the viability of early-passage RPMC was greater as compared with late passages, and the viability of late-passage RPMC was greater than that of mesothelioma cells. The amount of late-passage RPMC and mesothelioma cells able to form colonies in semisolid media was also drastically decreased in these conditions. These findings suggest that though macrophages can influence the process of asbestos-induced mesothelium transformation by different ways, as a whole the inhibitory action appears to be the strongest.