Cellular and molecular methods to study the role of gap junctional intercellular communication in toxicology.
Gap Junctional intercellular communication (GJIC) mediates the direct transfer of low-molecular weight factors from one cell to neighbouring ones. Since such factors include cAMP, inositol triphosphates and calcium, which are important messengers of signal transduction systems, G is believed to play a pivotal role in tissue homoeostasis. Its impairment is, therefore, likely to c functional defects in multicellular organisms. GJIC can be measured by several methods: (a) metaboli co-operation assay, (b) electrophysiological measurement, and (c) dye-transfer assay. At present, th dye-transfer assay is used in many laboratories since it can be applied easily with cultured cells a extended to in vivo situations with some modifications. In addition, molecular probes (cDNA and antibodies) for various connexin species have become available for studies of the molecular mechanis of GJIC modulation; connexins are structural proteins of gap junctions and cDNAs from at least 13 different connexin genes have been cloned. Many tumour-promoting agents have been shown to inhibit GJIC in cultured cells as well as in vivo. Increasing evidence suggests that connexin genes form of tumour suppressor genes and that various control mechanisms of GJIC are liable to disruption by carcinogenic agents.
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Unit of Multistage Carcinogenesis, International Agency for Research on Cancer, 150, cours Albert Thomas, F-69372 Lyon, Cedex 08, France.