Peroxynitrite (ONOO-), an anion and a potent oxidant, generated by the
interaction of nitric oxide (NO) and superoxide is able to induce apo
ptosis in HL-60 human leukemia cells in a time- and concentration-depe
ndent manner. Characteristic morphology of apoptosis can be observed 3
h after HL-60 cells are exposed to 10 mu M ONOO-. Treatment of HL-60
cells with increasing concentrations of ONOO- from 1 to 100 mu M confi
rms the concentration dependence of apoptosis as evidenced by: 1) degr
adation of nuclear DNA of these cells into integer multiples of approx
imately 200 base pairs; 2) colorimetric DNA fragmentation assay; and 3
) evidence of condensation of chromatin and nuclear fragmentation show
n by propidium iodide staining, Under the same conditions, peroxynitri
te causes apoptosis in another transformed cell line, U-937 cells, but
is ineffective at inducing apoptosis in normal endothelial cells deri
ved from human umbilical cord and normal human peripheral blood mononu
clear cells, This direct evidence of peroxynitrite inducing apoptosis
implicated a new function of this potent oxidant.