ACTIVATION OF A CALCIUM-MAGNESIUM INDEPENDENT ENDONUCLEASE IN HUMAN LEUKEMIC-CELL APOPTOSIS

Cytotoxic drugs induce apoptosis in human tumour cell lines and this i s characterised by fragmentation of the cell's DNA into nucleosome siz e units or multiples thereof In the present study we demonstrated that nuclei isolated from three human haemoatopoietic cell lines, HL-60, U 937 and K56Z contain an endonuclease that is independent of Ca++, Mg+ and Na+ ions for its activity. This contrasts with what has previosly been shown for a number of rodent cell types in which apoptosis has b een studied. The lack of ion sensitivity is also found in the nuclei o f peripheral blood granulocytes, indicating the data are not peculiar to cell lines. In addition, this patricular endonuclease activity does not appear to be sensitive to the endonuclease inhibitor aurintricarb oxylic acid. The previously demonstrated lack of calcium flux in HL-60 cells undergoing apoptosis, and the current demonstration of a lack o f an endonuclease dependent on this ion for its activity, suggest that the mechanism of apoptosis in human cells may be different from that in rodent cells.