Retinoids inhibit the mitogenic activity of tumourpromoting phorbol esters on human lymphocytes

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Abstract
The tumour-promoting agents 12-0-tetradecanoyl-phorbol-13-acetate (TPA) and phorbol-12,13-dibutyrate (PDB)1 are potent mitogens for human peripheral blood lymphocytes. In contrast, the non-cocarcinogenic substance phorbol lacks lymphocyte-activating properties. Non-toxic levels of retinoic acid (RA) or retinyl acetate (RAt) inhibit the phorbol-ester-induced lymphocyte proliferation. Selective inhibition of phorbol-ester-stimulated lymphocyte blastogenesis required the near-concurrent addition of retinoids. Differences in the sensitivity of phorbol-ester-stimulated lymphocyte subpopulations to the antagonistic action of RA or RAt, respectively, suggest that the inhibitory effect of retinoids may not be due to a common mode of action. Lymphocyte cultures may provide a useful model system for studies of the mechanisms of action of both phorbol esters and retinoids.