DIFFERENTIAL-EFFECTS OF CA2-60 CELL-NUCLEI( AND MG2+ ON ENDONUCLEASE ACTIVATION IN ISOLATED PROMYELOCYTIC HL)

In autodigestion assays, endonuclease activity in non-apoptotic HL-60 promyelocytic leukemia cell nuclei cleaved the chromatin of the autolo gous cells to an oligonucleosomal length pattern. Both EGTA and EDTA i nhibited the activation of endonuclease activity in isolated HL-60 cel l nuclei. The inhibition by EDTA could be reversed by exogenous Ca2+, but not by exogenous Mg2+. In Ca2+/Mg2+ -free nuclei digestion buffer, addition of Ca2+ (1-10 mmol/L) induced endonuclease activity in the i solated nuclei, while addition of Mg2+ had no effect. In the presence of Ca2+(O. 1 mmol/L), endonuclease activity was enhanced by exogenous Mg2+ (0.1-10 mmoI/L). These results suggest that the endonuclease resp onsible for internucleosomal DNA fragmentation in HL-60 cells during a poptosis is activated by Ca2+ and further modulated by Mg2+ in the pre sence of Ca2+.