Ultrastructure of nuclei of cisplatin-treated C6 glioma cells undergoing opoptosis

C6 glioma cells, treated with a cytostatic dose of cisplatin (1.66 x 10(-5) M) ceased dividing by 24 h and, most of them had undergone apoptosis by 72 -96 h, The reactive cells were classified into 5 types (T-I to V), accordin g to the ultrastructure of nuclei. At 4h, 20.4% of cells (T-I) showed minut e condensation and margination of chromatin, The nuclear envelope (NE) form ed slim and deep invaginations consisting of the inner or both membranes. T he later kind of NE invaginations often extended to the enlarged nucleoli a nd contained nucleolus-like material at ifs cytoplasmic side. Some nuclear pores were covered with a dome-shaped "cap" formed by fine filamentous mate rial. The number of T-I cells increased to 53.3% by 72 h. In T-II cells, wh ich appeared at 24 h, the chromatin was condensed into dense irregular mass es separated from the NE by a lucent space with filamentous structures prev enting complete margination of chromatin, Nucleoli of T-II cells were small and showed partial segregation of their components, The "capped" pores wer e absent in these apparently more damaged cells. From 24 h, cells with larg e and lobulated nuclei (T-m) started to increase in number and peaked at 72 h (6.6%). Except for some small lobules, the chromatin of T-II cells was m oderately aggregated and the NE was well preserved. Typical apoptotic cells with highly condensed and marginated chromatin (T-IV) peaked at 48-72 h (2 .4 - 4.8%). They appeared in 2 varieties, including cells with wrinkled nuc lei with less condensed and incompletely marginated chromatin or more lobul ated forms with highly condensed marginated chromatin suggesting their orig in from T-II or T-II cells, T-IV cells, as well as their fragments, underwe nt phagocytosis and secondary necrosis (T-V cells, 48.6% at 96 h). Two alte rnative routes of nuclear changes leading to cisplatin-triggered apoptosis, as represented by the sequence T-I-->T-III-->T-IV/V or T-I-->T-II-->T-IV/V , may explain the initially less or more damaged cells. These alternatives, together with progressive recruitment of reactive cells, suggest intrapopu lation differences in the sensitivity of cells or in the cell cycle perturb ations induced by cisplatin, Except for the T-IV and T-V cells, observed al terations of cytoplasmic organelles, including mitochondria, were fewer tha n reported in previous studies on cisplatin.