12-O-Tetradecanoyl Phorbol-13-acetate (TPA), the most powerful promoter in the phorbol series, initiates a series of metabolic events in granulocytes which are also activited during phagocytosis. Human promyloid cells derived from a patient with acute promyelocytic leukemia do not respond, or respond poorly to TPA. During in vitro maturation, the cells achieve ability to respond to TPA as measured by an increase in hexose-monophosphate stunt activity and protease production. On this basis we propose to study the development of TPA-responsive systems during the maturation of human myeloid cells in vitro to determine: 1) Whether the enzymatic activities involved in the response of granulocytes to TPA can be detected prior to development of TPA sensitivity; 2) whether other tumor promoters can induce the same responses: 3) whether all of the enzymatic activities involved in the TPA response appear simultaneously or sequentially: and 4) whether anti-inflammatory glucocorticoids have any selective effect on the expression of the enzymes involved in the TPA response. TPA-treated granulocytes are capable of inhibiting mitogen-induced lymphocyte activiation. We intend to determine whether this inhibitory activity is unique to TPA-treated granulocytes or whether it can be evoked by any agent which acitivates granulocytes to phagocytize, and to determine whether inhibition is mediated by cell-to-cell contact or by release of an inhibitory compound from treated granulocytes. Finally, we will evaluate each of the TPA-induced reactions in granulocytes in terms of suitability for use as bioassays utilizing normal human cells for detecting agents with promoter potential.