RETINOIC ACID INHIBITION OF COMITOGENIC ACTION OF MEZEREIN AND PHORBOL ESTERS IN BOVINE LYMPHOCYTES

  • 1 January 1978
    • journal article
    • research article
    • Vol. 38  (3) , 771-775
Abstract
12-o-Tetradecanoylphorbol-13-acetate (TPA) is an effective comitogen in phytohemagglutinin-treated bovine lymphocytes. Concurrent addition of 10-8 M TPA gave a greater than 6-fold increase in DNA synthesis over cultures treated with the lectin alone. The delayed addition of phorbol ester, relative to the start of the lectin treatment, eliminated this synergistic action. Structure-function studies showed that the comitogenic activity of different phorbol diesters ran parallel to their tumor-promoting activity. A nontoxic level (50 .mu.M) of retinoic acid selectively antagonized this synergistic effect of phorbol ester. This inhibitory action required the near-concurrent addition of retinoic acid with TPA. The TPA-mediated induction of RNA and protein synthesis was unaffected by retinoic acid. A number of natural and synthetic retinoids were evaluated. None were as inhibitory as was retinoic acid. Lymphocyte cultures appeared to provide a useful system for exploring the mechanisms of action of TPA and retinoic acid.