Inhibition of the mixed lymphocyte proliferative response by phorbol esters.

The phorbol diester, 12-O-tetradecanoyl-phorbol-13-acetate, a potent cocarcinogen in mice, blocks the induction of DNA synthesis in lymphocytes undergoing the mixed lymphocyte response. At 10(-7) M diester, the induced DNA synthesis is inhibited almost completely (99%). This action of the diester affects some early step in the response which is necessary for the triggering of cell replication; on-going DNA replication is not significantly affected. Phorbol 12,13-diacetate, a less potent analogue in tumor promotion in vivo, is also a less potent inhibitor of the mixed lymphocyte response (75% inhibition at 10(-6) M). Phorbol, the parent alcohol, is not effective in either system. The use of phorbol diesters in the molecular dissection of mixed lymphocyte responses is discussed.