Molt-4 human leukemia cells were triggered to apoptosis by various agents w
ith different mechanisms of action. Staurosporine, a protein kinase C (PKC)
inhibitor; camptothecin, a topoisomerase I blocking drug; and tiazofurin,
an inhibitor of inosine 5'-phosphate dehydrogenase (IMPDH), were used. Ultr
astructural analysis showed morphologic changes characteristic of apoptosis
that were very similar for all three agents. Nevertheless, DNA oligonucleo
somic fragmentation was not detectable by agarose gel electrophoresis. Howe
ver, a genomic DNA cleavage appeared after pulse-field gel electrophoresis
(PFGE) in cells treated with these agents for 24 h. Furthermore, in situ ni
ck translation (NT) showed a finely spotted nuclear labelling in staurospor
ine-treated cells and a compact fluorescence after camptothecin incubation.
In tiazofurin-treated cells an intermediate pattern was found. Therefore,
apoptotic agents with different mechanisms of action induced the formation
of large genomic DNA fragments and very similar ultrastructural changes. Th
erefore, both phenomena and the closely related apoptosis progression depen
d on target cell machinery and not on the triggering agent.