CA2+ MG2+-DEPENDENT ENDONUCLEASE ACTIVATION IS AN EARLY EVENT IN VP-16-INDUCED APOPTOSIS OF HUMAN BREAST-CANCER MCF7 CELLS IN-VITRO/

Apoptosis is now recognized as one of the major processes regulating t he size of cell populations. However, despite intensive investigations the biochemical and enzymological mechanisms involved in apoptosis re main unclear. In the present study we demonstrate activation of a Ca2/Mg2+-dependent endonuclease during VP-16-induced apoptosis in MCF7 ce lls. Nuclease activation occurred prior to the appearance of internucl eosomal DNA fragmentation, suggesting that this activation may be an e arly and possibly critical step in drug-induced apoptosis. Analysis of the internucleosomal DNA fragments showed that they contained phospho rylated 5'-ends, indicating that they were produced by a Ca2+/Mg2+-dep endent endonuclease.