DYNAMICS OF APOPTOTIC EVENTS INDUCED IN H UMAN LEUKEMIA U-937 CELLS BY TUMOR-NECROSIS-FACTOR

The nature and sequence of cell events associated with TNF-induced apo ptosis were studied in human leukemic U-937 cells. It was shown that t he earliest changes include cell distrophy and condensation, inhibitio n of nucleic acids synthesis and DNA fragmentation. Significant injury of cell mitotic apparatus, associated with G(2)/M cell arrest, may be also attributed to early alteration. This effect suggests that TNF-in duced apoptosis in U-937 cells may result from ''mitotic catastrophe'' . These events are followed by an increased expression of some differe ntiation markers (CD15, CD45RA) as well as Ki-67 and BCL-2 antigenes. A sharp decrease of surface transferrin receptor (TfR) expression was found in the last period of TNF treatment. Important is the fact that TNF-induced apoptosis does not discriminate the cells with various lev els of differentiation and TfR expression. It was shown that during th e first days even TNF-resistant cell population was formed during apop tosis. Possible molecular mechanisms of TNF-induced apoptosis are disc ussed.