GAP JUNCTIONAL INTERCELLULAR COMMUNICATION OF PRIMARY AND ASBESTOS-ASSOCIATED MALIGNANT HUMAN MESOTHELIAL CELLS

We examined gap junctional intercellular communication (GJIC) of prima ry human mesothelial cells and cell lines of asbestos-associated human pleural mesotheliomas, and the effect of asbestos and other mineral f ibres on these cells. In homologous cultures, the GJIC capacity of six out of seven tumour cell lines was markedly less than for primary mes othelial cells. This defect in GJIC appeared not to be at the expressi on level of mRNA and protein of the gene encoding the 43 kDa gap junct ion protein. In heterologous cocultures of tumour cells and primary me sothelial cells, however, 80-90% of the tumour cell/normal cell contac ts were functional. Exposure of primary mesothelial cells to TPA, a ph orbol ester tumour promoter, resulted in marked inhibition of GJIC, be ing an action common to numerous tumour promoters. Such an effect thou gh was not observed with the carcinogenic mesothelioma-inducing minera l fibres chrysotile and amosite, neither with glass wool. These result s suggest that a permanent defect in GJIC capacity is a common feature of human mesothelioma cells, but how mineral fibres are involved in t he process of mesotheliomagenesis is still unclear.