Activation of a calcium magnesium independent endonuclease in human leukemic cell apoptosis

Cytotoxic drugs induce apoptosis in human tumour cell lines and this is characterised by fragmentation of the cell's DNA into nucleosome size units or multiples thereof. In the present study we demonstrated that nuclei isolated from three human haematopoietic cell lines, HL-60, U937 and K562, contain an endonuclease that is independent of Ca++, Mg++ and Na+ ions for its activity. This contrasts with what has previously been shown for a number of rodent cell types in which apoptosis has been studied. The lack of ion sensitivity is also found in the nuclei of peripheral blood granulocytes, indicating the data are not peculiar to cell lines. In addition, this particular endonuclease activity does not appear to be sensitive to the endonuclease inhibitor aurintricarboxylic acid. The previously demonstrated lack of calcium flux in HL-60 cells undergoing apoptosis, and the current demonstration of a lack of 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.