MODULATION OF APOPTOSIS SIGNALING IN ETOPOSIDE-TREATED LYMPHOMA-CELLS

Signals of etoposide (ETO) induced apoptosis were studied in a human ( B) lymphoma cell line, HT58. Morphology and DNA fragmentation assays p roved the appearance of apoptosis after a short ETO treatment (4 hours ). Modulation of signal components of this apoptotic pathway resulted the following a) phorbol ester (PMA) or heat shock inhibited apoptosis , which was prevented by staurosporine b) 3-aminobenzamide, a potent p oly(ADP-ribose)polymerase inhibitor, had no significant effect; c) cys teine reactive compounds, such as iodoacetamide and phenylarsine oxide , as well as protease inhibitor TPCK were very active inhibitors of ap optosis; d) protein synthesis inhibitor, cycloheximide, potentiated ce ll death; e) the ETO-induced p53 protein overexpression had neither en hancing nor protecting effect on the apoptotic process. In conclusion, in the majority of HT58 lymphoma cells the apoptotic machinery is ''p rimed'' (the components are already expressed) and ETO-induced apoptos is is regulated by STA sensitive phosphorylation and proteolysis by cy stein proteases,but riot affected by ADP-ribozylation or p53.