EFFECTS OF SELECTED ANTI-TUMOR-PROMOTING CHEMICALS ON METABOLIC COOPERATION BETWEEN CHINESE-HAMSTER V79 CELLS

Many tumor-promoting chemicals inhibit gap junctional communication be tween cells. We investigated the possibility that antipromoting chemic als may act inversely and enhance gap junctional communication. The V7 9/metabolic cooperation assay is an in vitro test that measures gap ju nctional communication indirectly by determining the extent of metabol ic cooperation between mutant and wild-type V79 Chinese hamster lung f ibroblasts in culture. Six in vivo antipromoters (caffeine, 3-isobutyl -1-methylxanthine (IBMX), phenidone, dibromoacetophenone, tosylphenyla lanine chloromethyl ketone (TPCK), and acetic acid) were tested in thi s assay to assess their effects on metabolic cooperation. Caffeine, IB MX, phenidone, and dibremoacetophenone had no effect on metabolic coop eration, while TPCK slightly inhibited metabolic cooperation in one V7 9 assay. Acetic acid appeared to facilitate metabolic cooperation. In tests where an antipromoter was combined with the established tumor pr omoter phorbol 12-myristate 13-acetate (PMA), acetic acid, caffeine, a nd IBMX counteracted PMA-induced inhibition of metabolic cooperation, while phenidone, dibromoacetophenone, and TPCK had little effect. Thes e results indicate that some antipromoters interfere with the ability of a tumor-promoting chemical to inhibit metabolic cooperation and sug gest that alteration of gap junctional communication can be a mechanis m of antipromoter action. (C) 1994 Academic Press, Inc.