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Effect of Maturation on the Response of Human Promyelocytic Leukemia Cells (HL-60) to the Tumor Promoter 12-O-Tetradecanoylphorbol-13-acetate¹

Departments of Biochemistry [N. M., J. K. C., G. A.], Pediatrics [J. K. C., G. A.], and Medicine [H. S. G.], Mount Sinai School of Medicine, City University of New York, New York, New York 10029

Exposure of circulating human granulocytes to the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate, stimulates a number of biochemical reactions normally associated with the phagocytic process, including superoxide anion production and oxidation of glucose via the hexose monophosphate shunt. Cells of the human promyelocytic line, HL-60, develop a number of the morphological and functional characteristics of mature granulocytes during growth in the presence of dimethyl sulfoxide. We report here that the ability of HL-60 cells to respond to 12-O-tetradecanoylphorbol-13-acetate with increased oxidative metabolism depends on the extent to which they have matured. Evidence is presented indicating that the increased responsiveness of the cells is associated with an increase in the proportion of cells in the population with a membrane-bound, 12-O-tetradecanoylphorbol-13-acetate-activated reduced nicotinamide adenine dinucleotide phosphate oxidase. It is further demonstrated that an increase in the proportion of cells bearing complement receptors, a characteristic of mature myeloid cells, coincides with the observed increase in cells with 12-O-tetradecanoylphorbol-13-acetate-activated reduced nicotinamide adenine dinucleotide phosphate oxidase. We find, however, that only some of the responses of HL-60 cells to 12-O-tetradecanoylphorbol-13-acetate require maturation. The tumor promoter enhances release of proteolytic enzymes by these cells to the same extent, whether or not they have been allowed to mature in the presence of dimethyl sulfoxide. If, as has been postulated, tumor promoters act by binding to specific cellular receptors, our results imply that these compounds can interact with more than one type of receptor in the same cell and that at least one form of receptor is present in HL-60 cells before maturation.

¹ This work was supported in part by NIH Grants CA 16890 and CA 25985 from the National Cancer Institute and Grants PDT-83K and BC-322 from the American Cancer Society.

² Postdoctoral Fellow of the USPHS. To whom requests for reprints should be addressed.

³ Senior Investigator of the New York Heart Association.

Received 5/29/79. Accepted 1/16/80.