Dimethyl sulfoxide (DMSO), which induces differentiation of myeloid ce
lls, was found to cause apoptosis in human leukemic U937 cells. Apopto
sis was assessed by DNA electrophoresis and flow cytometry. The time n
eeded to induce apoptosis varied from a few hours to 2-3 days, dependi
ng on the concentration of DMSO used. The plasma membrane remained int
act long after DNA fragmentation had occurred. DMSO-induced apoptosis
was inhibited by zinc ions and, to a lesser extent, by the protein kin
ase C activator: phorbol 12-myristate 13-acetate (PMA), Cycloheximide
and actinomycin D did not prevent DMSO-induced apoptosis, showing that
U937 cells do not require protein or RNA synthesis to undergo apoptos
is. DMSO induced apoptosis despite the expression of the anti-apoptoti
c Bcl-2 protein in U937 cells, The amount of Bcl-2 remained unchanged
during DMSO-induced apoptosis.