Biological effects of asbestos fibres on rat lung maintained in vitro

The in vitro systems used to determine whether asbestos acts as an initiator or as a promoter have failed to give definitive answers. We studied the effect of chrysotile and crocidolite in an initiation-promotion model on the Fischer rat embryo lung. Two assay systems were used in succession: organ culture of the lung cultured for 24 days and epithelial cell culture derived from treated or untreated explants cultured for 25 passages. Apart from the control groups, three major groups were analysed: (1) fibres with complete carcinogenic potency: explants and/or cells treated with fibres alone; (2) fibres with initiating potency; short treatment with fibres, followed by treatment with the classical promoter TPA; (3) fibres with promoting potency: short benzo[a]pyrene treatment followed by treatment with the fibres. In organ culture, fibres alone induce only cytotoxic lesions; in the 'fibres with promoting potency' group, precancerous lesions were observed. In epithelial cell culture, several transformation criteria are analysed. Our results with the cell system confirm that fibres act as a promoter, but also as a complete carcinogen. However, for equal doses, crocidolite needs a longer treatment time than chrysotile. These different assays failed to demonstrate any initiating activity of the fibres. The use of organ and cell culture in succession makes it possible to demonstrate the in vitro promoting effect of chrysotile and crocidolite.