Inhibitory effect of tumor promoting phorbol esters and mezerein on human mixed lymphocyte reaction.

The effect of phorbol ester-type tumor promoters on the mixed reaction of human lymphocytes was investigated. When a low concentration (10 ng/ml, 1.67 X 10(-8) M) of 12-O-tetradecanoylphorbol-13-acetate (TPA) was added at the beginning of the mixed lymphocyte reaction, this, as measured by [3H]thymidine incorporation, was almost completely inhibited. The inhibitory effect is apparently not related to a toxic effect, since [3H]uridine incorporation was affected to a lesser extent by the addition of TPA. TPA is also inhibitory when added after the reaction has started. The inhibition of the reaction by TPA is very rapid and complete inhibition can be seen within 2 h after TPA addition. Another promoting phorbol ester, phorbol-12,13-didecanoate )PDD), also inhibited the reaction, whereas inactive derivatives, phorbol and 4 alpha-PDD, did not. Mezerein, a weak promoter on mouse skin, was also a potent inhibitor of the human mixed lymphocyte reaction.