EFFECT OF PERCHLOROETHYLENE AND ITS METABOLITES ON INTERCELLULAR COMMUNICATION IN CLONE-9 RAT-LIVER CELLS

Cap junction intercellular communication (IC) is thought to be importa nt in chemical carcinogenesis as abnormalities in IC have been found i n cancer cells. Perchloroethylene (PERC) is metabolized in rodent live r to dichloroacetic acid (DCA) and trichloroacetic acid (TCA), which a re rodent liver carcinogens. Chloral hydrate (CH) and trichloroethanol (TCEth) are kidney metabolites. We used Lucifer yellow scrape-load dy e 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 exposu re times of 1, 4, 6, 24, 48, and 168 h. Concentrations for each chemic al varied and were based on preliminary data on effect and cytotoxicit y. To compare the relative effectiveness of each chemical to cause bio logical change, we identified the lowest concentration and shortest ti me to significantly reduce dye transfer. DCA caused a significant chan ge 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 effi ciencies, as defined by the concentration needed to produce 50% reduct ion 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 TCEt h exhibited variances from these results and may indicate specific cel l responses to these chemicals. The mechanism(s) responsible for inhib ition of IC by these structurally related chemicals needs to be establ ished.