INHIBITION OF INTERCELLULAR COMMUNICATION IN RAT HEPATOCYTES BY PHENOBARBITAL, 1,1,1-TRICHLORO-2,2-BIS(P-CHLOROPHENYL)ETHANE (DDT) AND GAMMA-HEXACHLOROCYCLOHEXANE (LINDANE) - MODIFICATION BY ANTIOXIDANTS AND INHIBITORS OF CYCLOOXYGENASE

Several tumour promoting chemicals have been shown to inhibit intercel lular communication (IC) through gap junctions in cell cultures. In th e present investigation we studied the effect of the hepatic tumour pr omoters phenobarbital (PB), 1,1,1-trichloro-2,2-(p-chlorophenyl)ethane (DDT) and gamma-hexachlorocyclohexane (lindane) on IC in rat hepatocy te cultures. IC was evaluated by microinjection of fluorescent Lucifer Yellow CH dye and visualization of dye spread to adjacent hepatocytes . Incubation of hepatocytes with PB (2 mM), DDT (30 muM) and lindane ( 25 muM) decreased dye-coupling of the cells by about 30%, 42% and 35%, respectively; dye-coupling in untreated cultures was 88.1+/-0.7%. Inh ibition of IC was reversible when the xenobiotics were removed from th e medium. The antioxidant vitamin E (100 muM) prevented inhibition of dye-coupling by PB and lindane and partially that by DDT. Superoxide d ismutase (100 units/mul) counteracted the effect on dye-coupling by PB , but not that by the insecticides. Similarly, the cyclo-oxygenase inh ibitors indomethacin and aspirin only reversed the effect of PB on IC, but not that of DDT or lindane. As indicated by further experiments, prevention by non-steroidal anti-inflammatory agents of PB-induced inh ibition of IC is most likely not mediated by inhibition of cyclo-oxyge nase. The results indicate significant differences in the action of PB , DDT and lindane on IC in hepatocyte cultures. This is suggested by t he differential effects of superoxide dismutase and non-steroidal anti -inflammatory agents on the action of the three tumour promoting chemi cals. Whereas superoxide radicals may be involved in the inhibition of dye-coupling by PB, radical intermediates of the insecticides may be responsible for the decrease in dye-coupling by DDT and lindane.