title: Mechanism of phorbol myristate acetate-induced lymphotoxin production by a human T cell hybridoma.
abstract: Various hydroxyl radical scavengers markedly inhibited phorbol myristate acetate (PMA)-induced lymphotoxin (LT) production by a human T cell hybridoma, AC5-8. Among those we tested, tetramethylurea (TMU) was the most potent scavenger, and it was revealed that TMU must be added before 2 h have elapsed after PMA addition in order for LT production to be inhibited. In concordance with this fact, soluble NADPH dependent O2- forming enzyme(s) were activated several fold by PMA. PMA also induced DNA strand breaks, a process markedly inhibited by TMU. As expected, ADP-ribosyl transferase (ADPRT), which is well known to require DNA strand breaks for its enzymatic activity, was activated by PMA treatment. In addition, specific inhibitors for ADPRT, namely 3-amino-benzamide and nicotinamide, inhibited PMA-induced LT production. Taken together, these three successive events, activation of soluble NADPH dependent O2- forming enzyme(s), DNA strand breaks and activation of ADPRT, may be required for PMA-induced LT production by AC5-8.
mesh_terms: D002460:Cell Line; D006801:Humans; D006825:Hybridomas / Q000187:drug effects / Q000276:immunology*; D007700:Kinetics; D007945:Leukemia, Lymphoid; D008233:Lymphotoxin-alpha / Q000096:biosynthesis*; D010704:Phorbols / Q000633:toxicity*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D008233:Lymphotoxin-alpha; D010704:Phorbols; D013755:Tetradecanoylphorbol Acetate