Retinole Acid Inhibition of the Comitogenic Action of Mezerein and Phorbol Esters in Bovine Lymphocytes1

12-O-Tetradecanoylphorbol-13-acetate (TPA) is an ef fective comitogen in phytohemagglutinin-treated bovine lymphocytes. Concurrent addition of 10 8 MTPA gives a greater than 6-fold increase in DNA synthesis over cul tures treated with the lectin alone. The delayed addition of phorbol ester, relative to the start of the lectin treat ment, eliminates this synergistic action. Structure-func tion studies show that the comitogenic activity of different phorbol diesters runs parallel to their tumor-promoting activity. A nontoxic level (50 /¿M) of retinole acid selec tively antagonizes this synergistic effect of phorbol ester. This inhibitory action requires the near-concurrent addi tion of retinole acid with TPA. In contrast, the TPA-mediated induction of RNA and protein synthesis is unaf fected by retinoic acid. A number of natural and synthetic retinoids were evaluated; none were as inhibitory as was retinoic acid. Lymphocyte cultures appear to provide a useful system for exploring the mechanisms of action of both TPA and retinoic acid.