Mechanisms of death induced by cisplatin in proximal tubular
epithelial cells: apoptosis versus necrosis.
Lieberthal, Wilfred, Veronica Triaca, and Jerrold Levine.
Renal Section, Evans Memorial Department of Clinical Research and
Department of Medicine, Boston University Medical Center Hospital,
Bostan, MA 02118
APStracts 3:0020F, 1996.
We have examined the mechanisms of cell death induced by cisplatin in
primary cultures of mouse proximal tubular cells. High concentrations
of cisplatin (800 [mu]M) led to necrotic cell death over a few hours.
Much lower concentrations of cisplatin (8 [mu]M) led to apoptosis
which caused loss of the cell monolayer over several days. Necrosis
was characterized by cytosolic swelling and early loss of plasma
membrane integrity. In contrast, early features of cells undergoing
apoptosis included cell shrinkage and loss of attachment to the
monolayer. Nuclear chromatin became condensed and fragmented in
apoptosing cells. These features were absent in necrotic cells. DNA
electrophoresis of cell exposed to 800mM cisplatin yielded a
"smear" pattern, due to random DNA degradation. In contrast,
the DNA of apoptosing cells demonstrated the "ladder" pattern
resulting from internucleosomal DNA cleavage. Anti-oxidants delayed
ciplatin-induced apoptosis but not necrosis. Thus, the mechanism of
cell death induced by cisplatin is concentration dependent. Reactive
oxygen species play a role in mediating apoptosis but not necrosis
induced by cisplatin.
Received 27 October 1995; accepted in final form 2 January 1996.
APS Manuscript Number F367-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 29 January 96