The effects of retinoic acid and a tumor promoter, 12-O-tetra-decanoylphorbol-13-acetate, on lymphocyte proliferation

The tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) inhibits DNA synthesis in allogenic, mixed cultures of bovine lymphocytes. Retinoic acid, an antagonist of TPA in in vivo skin promotion, was tested for its ability to counteract the effect of TPA on lymphocyte proliferation. Retinoic acid or related compounds, retinol or retinol actetate, did not reverse or prevent the inhibitory effect of TPA. Instead retinoic acid also inhibited DNA synthesis in mixed lymphocyte cultures. On the average, about 8 μM retinoic acid inhibited the mixed lymphocyte response by 50%. The mitogenic response of lymphocytes to phytohemagglutinin (PHA) was also inhibited by retinoic acid. The degree of inhibition depended both on the concentration of PHA and of retinoic acid. Therefore, in regard to bovine lymphocytes, retinoic acid depresses DNA synthesis in both allogenic and lectin stimulated responses. Such suppression should be taken into account in the use of retinoic acid in chemotherapy.