TUMOR-PROMOTING DITERPENE ESTERS INDUCE MACROPHAGE DIFFERENTIATION, BUT PREVENT ACTIVATION FOR TUMORICIDAL ACTIVITY OF MACROPHAGE AND NK CELLS

Abstract

This chapter discusses the tumor-promoting Diterpene esters inducing macrophage differentiation. Tumor-promoting diterpene esters facilitate the formation of tumors in the skin of mice treated with subthreshold doses of chemical carcinogen. Tumor promoters elicit a considerable array of in vitro effects on cells in culture, often in opposing ways. Among other attributes, tumor promoters stimulate DNA synthesis, initiate proliferation in various cell types, induce various enzymes, and evoke changes in cell membranes and chromosomal damage. Tumor promoters also affect mononuclear phagocytes at the differentiation and effector levels, and with opposing consequences. The tumor-promoting phorbol ester, 12-0-tetradecanoyl-phorbol-13-acetate (TPA), induces in bone marrow cells the proliferation and differentiation of precursors of the mononuclear phagocyte lineage. TPA initiates DNA synthesis and cell proliferation in some but by no means all marrow cells. In parallel, the small, round, floating cells increasingly adhere to the substratum and spread, finally attaining a considerable size. DNA synthesis is especially active in the early phase of adherence and spreading.