Changes in cytosolic CA2+ are not involved in DDT-induced loss of gap junctional communication in WB-F344 cells.
Recent studies have demonstrated that the insecticide DDT is a tumor promoting agent. Similar to many other tumor promoting agents, DDT has been shown to inhibit gap junctional intercellular communication (GJIC) between cells in culture, and it has been suggested that DDT-induced loss of communication between adjacent cells may depend on changes in cytosolic free Ca2+ concentration [( Ca2+]i). In the present study, the role of [Ca2+]i in DDT-induced loss of GJIC was investigated in WB-F344 in rat liver cells using the scrape-loading/dye transfer assay (SLDT) and the Ca2+ fluorescent indicator, fura-2. Our results show that DDT at noncytotoxic concentrations caused a reversible loss of GJIC. Inhibition of GJIC was not associated with detectable increases in [Ca2+]i, and was not prevented by loading cells with the intracellular Ca2+ chelator, BAPTA. In addition, the hydroquinone, tBuBHQ, which caused a 2-3 fold sustained increase in [Ca2+]i, did not inhibit GJIC. Conversely, when untreated cells were loaded with increasing BAPTA concentrations, GJIC were lost. These results indicate that increases in [Ca2+]i are not responsible for DDT-induced loss of communication and that, in general, an increase in [Ca2+]i within physiological levels is not sufficient to abolish GJIC. However, Ca2(+)-dependent processes that are active at normal resting [Ca2+]i appear to be required for the maintenance of GJIC.
Fransson
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R
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Nicotera
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P
Wärngård
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L
Ahlborg
U G
UG
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D003634:DDT / Q000633:toxicity*; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D016257:Fura-2; D007365:Intercellular Junctions / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D051381:Rats
D001572:Benzofurans; D004533:Egtazic Acid; D003634:DDT; D007770:L-Lactate Dehydrogenase; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium; D016257:Fura-2