INHIBITION OF INTERCELLULAR COMMUNICATION BY CONDENSATES OF HIGH AND LOW TAR CIGARETTES

Inhibition of gap junctional intercellular communication (GJIC) is a p redictive short term test for tumor promoting activity. A new metaboli c cooperation assay has been developed, which takes the cytochrome P-4 50 metabolism into account. In this assay the inhibitory activity of t obacco smoke condensates (CSC) and CSC fractions from high and low tar cigarettes was tested, CSC of both high and low tar cigarettes and fr actions thereof contained tumor promoting activity. The tar yield of t he cigarettes did not closely reflect the effects in the GJIC assay an d the major constituent nicotine had no effect. The effect was only ma rginally greater in cells expressing different cytochrome P-450 enzyme s, indicating that the active substances are not metabolized by these enzymes. The activities of CSC fractions were considerably lower than the activities in the unfractionated CSC. This may indicate that compo unds in the CSC act strongly synergistically. Furthermore, CSC and CSC fractions synergistically inhibit GJIC with the tumor promoter 12-O-t etradecanoylphorbol-13-acetate, indicating different mechanisms of act ion.