Production of a cytotoxin from phorbol myristate acetate-treated human promyelocytes.
Human promyelocytic leukemia cells, when differentiated into macrophages by treatment with phorbol myristate acetate, secrete a cytolytic factor. Enhanced production was achieved when the cultures were treated with bacterial lipopolysaccharide (LPS). Production of the factor was inhibited when cultures were treated with dactinomycin immediately after LPS treatment. Tritirachium alkaline proteinase treatment inactivated the factor, indicating that it has an essential protein moiety. The molecular weight was found to be approximately 40,000 by Sephacryl S-200 gel filtration. The factor was stable at 56 degrees C for 30 minutes, but 80% of the activity was inactivated at 70 degrees C in 30 minutes. The factor was destroyed (96%) by dialysis against 0.01 M HCl (pH 2) for 14 hours. The cytolytic factor had little activity on normal fibroblasts, but it was able to significantly kill transformed cells in vitro.
D000818:Animals; D002460:Cell Line; D003603:Cytotoxins / Q000096:biosynthesis*; D003609:Dactinomycin / Q000494:pharmacology; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D006367:HeLa Cells / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D007739:L Cells / Q000187:drug effects / Q000502:physiology; D015470:Leukemia, Myeloid, Acute / Q000503:physiopathology*; D051379:Mice; D010704:Phorbols / Q000633:toxicity*; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
D003603:Cytotoxins; D010704:Phorbols; D003609:Dactinomycin; D013755:Tetradecanoylphorbol Acetate