Effect of perchloroethylene and its metabolites on intercellular communication in clone 9 rat liver cells.
Gap junction intercellular communication (IC) is thought to be important in chemical carcinogenesis as abnormalities in IC have been found in cancer cells. Perchloroethylene (PERC) is metabolized in rodent liver to dichloroacetic acid (DCA) and trichloroacetic acid (TCA), which are rodent liver carcinogens. Chloral hydrate (CH) and trichloroethanol (TCEth) are kidney metabolites. We used Lucifer yellow scrape-load dye transfer as a measure of IC to look at the effect of PERC, DCA, TCA, CH, and TCEth on Clone 9 cell cultures (normal rat liver cells). Four independent experiments were performed for each chemical using exposure times of 1, 4, 6, 24, 48, and 168 h. Concentrations for each chemical varied and were based on preliminary data on effect and cytotoxicity. To compare the relative effectiveness of each chemical to cause biological change, we identified the lowest concentration and shortest time to significantly reduce dye transfer. DCA caused a significant change at 10 mM at 6 h; TCA, 1 mM at 1 h; CH and TCEth, 1 mM at 24 h; and PERC, 0.01 mM at 48 h. Over a 24-h treatment period, the relative efficiencies, as defined by the concentration needed to produce 50% reduction in IC, were PERC (0.3 mM) >> TCA (3.8 mM) > TCEth (6.6 mM) = CH (7.0 mM) >> DCA (41 mM). Time-course data indicated that PERC, DCA, and TCA produced reduction in IC in a similar fashion, but 5 mM CH or TCEth exhibited variances from these results and may indicate specific cell responses to these chemicals. The mechanism(s) responsible for inhibition of IC by these structurally related chemicals needs to be established.
Benane
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U.S. Environmental Protection Agency, National Health and Environmental Effects Research Laboratory, Research Triangle Park, North Carolina 27711, USA.
Blackman
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House
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D000704:Analysis of Variance; D000818:Animals; D002697:Chloral Hydrate / Q000633:toxicity; D002999:Clone Cells; D003999:Dichloroacetic Acid / Q000633:toxicity; D005023:Ethylene Chlorohydrin / Q000031:analogs & derivatives / Q000633:toxicity; D017629:Gap Junctions / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013750:Tetrachloroethylene / Q000378:metabolism / Q000633:toxicity*; D014238:Trichloroacetic Acid / Q000633:toxicity; D014873:Water Pollutants / Q000378:metabolism / Q000633:toxicity*
D014873:Water Pollutants; D002697:Chloral Hydrate; D014238:Trichloroacetic Acid; D005023:Ethylene Chlorohydrin; D003999:Dichloroacetic Acid; C005849:2,2,2-trichloroethanol; D013750:Tetrachloroethylene