Publication: Cisplatin treatment of NIH-3T3 cultures induces a form of autophagic death in polyploid cells
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Date
2008
Authors
Spano, Alessandra ; Monaco, Gianni ; Barni, Sergio ; Sciola, Luigi
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The effects induced by different
concentrations (50, 75, 100 μM) of the cytostatic drug
cisplatin (cDDP) in NIH/3T3 cells were analyzed. Subconfluent
cultures of this mouse fibroblast line, obtained
after serum deprivation, showed the presence of
aneuploid/polyploid cells with ploidy values ranging
from 4c to 24c. DNA content cytofluorometry
demonstrated that 50 and 75 μM cDDP induced a
cytostatic effect; 100 μM concentration showed lower
antiproliferative action. All treatments caused a partial
cell detachment and apoptosis, the incidence of which
appeared to be cDDP concentration-dependent.
Ultrastructural and fluorescence microscopy integrated
analyses of the still adherent cells demonstrated the
presence of alternative degeneration patterns, especially
in polyploid cells, with extensive modifications at both
nuclear and cytoplasmic levels. There were events of
micronucleation and phenomena of multilobulation and
furrows of the nucleus that preceded the formation of
heterogeneous fragments. These events were correlated,
at cytoplasmic level, with actin reorganization and the
appearance of autophagocytotic processes. In our cell
model, the same pharmacological treatment was able to
induce different cell death phenomena relating to cell
dimension and ploidy. More actively proliferating cells (2c–4c DNA content) die throughout canonical
apoptosis, while polyploid cells prevailingly degenerate
by mechanisms partly referable to autophagic cell death.
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