CELL-DEATH INDUCED BY VINCRISTINE IN THE INTESTINAL CRYPTS OF MICE AND IN A HUMAN BURKITTS-LYMPHOMA CELL-LINE

Although vincristine is widely used clinically in the treatment of some human cancers, its mechanism of action has not been clearly established. In this study, the patterns of cell death induced by vincristine in the intestinal crypts of mice and in a human Burkitt's lymphoma cell line were investigated by light and electron microscopy. Vincristine was found to enhance apoptosis of interphase cells in both systems and also to cause the arrest of cells in mitosis, the latter effect being more pronounced in the intestinal crypts. Arrested mitotic cells went on to die by a process that had a number of features in common with apoptosis. These include compaction of chromatin (following coalescence of chromosomes), condensation of the cytoplasm, initial preservation of organelle integrity, and eventually the fragmentation of the cell into a number of membrane-enclosed bodies which are morphologically similar to conventional apoptotic bodies. The results suggest that the cytocidal effect of vincristine is not solely dependent on metaphase arrest but is a cumulative one, resulting both from apoptosis of interphase cells and the 'apoptotic-like' death of cells arrested in metaphase.