DIFFERENTIAL DOSE-DEPENDENT EFFECTS OF ALPHA-CAROTENE, BETA-CAROTENE AND LYCOPENE ON GAP-JUNCTIONAL INTERCELLULAR COMMUNICATION IN RAT-LIVER IN-VIVO

In order to examine the relevance of alteration of gap-junctional inte rcellular communication (GJIC) to chemopreventive activity against car cinogenesis, the effects of alpha- and beta-carotene as well as lycope ne, typical chemopreventive carotenoids, on cell coupling via gap junc tions in rat liver in vivo were studied using a direct functional dye- transfer technique. We found that all three test compounds given at a dose of 50 mg/kg-body weight (b.w.) daily, 5 times by gavage, inhibite d GJIC, while similar treatment with 5 mg/kg b.w. caused enhancement, especially in the beta-carotene- and lycopene-treated groups. At the d ose level of 0.5 mg/kg b.w., the three compounds had no effect. The fi ndings show that all three agents differentially modulate GJIC dependi ng on the dose, with beneficial effects on cell communication only det ected at the one dose. The result suggests that determination of the d ose of chemicals to be used is crucial for human intervention studies.