1. Apoptosis as the mechanism of cell death induced by a new cytotoxic and anticancer agent (
N.C.1213) was investigated by morphological and biochemical criteria in human Jurkat T
leukemia cells. 2. The effect of
N.C.1213 on the survival of Jurkat T, LV-50,
H-9, and Molt-3 cells was measured. Jurkat T cells exhibited the highest response, with less than 10% of the cells remaining viable after exposure to 10 microM
N.C.1213 for a 24 hr period. All other cell cultures were also affected but to a lesser extent. 3. With the use of a fluorescence microscope, several morphological features characteristic of apoptosis such as condensed
chromatin and apoptotic bodies were identified in Jurkat T cells after exposure to
N.C.1213 and
melphalan. The results indicated that
melphalan was more cytotoxic than
N.C.1213 as shown by the dye exclusion test. However,
N.C.1213 showed a greater apoptotic index than
melphalan. The IC50 of
N.C.1213 in Jurkat T cells was determined to be 3.5 microM. 4.
A DNA ladder (fragmentation of
DNA into multimers of approximately 200 base pairs), which is one characteristic feature of apoptosis, was not detected when Jurkat T cells were exposed to
N.C.1213. Hence it is probable that the key morphological events in apoptosis observed in the present experimental conditions precede the internucleosomal cleavage of
DNA.