Drug-induced necrosis

Tyson tyson at canada.com
Sun Nov 21 12:11:28 EST 1999

....good luck...you'll need it!....here's an interesting article which might
help answer your question....

"Aponecrosis: Morphological and biochemical exploration of a syncretic
process of cell death sharing apoptosis and necrosis."

J Cell Physiol 2000 Jan;182(1):41-49

ABSTRACT: A rat fibroblastic cell line (rat-1/myc-ERtrade mark) was treated
with different concentration of Antimycin A, a metabolic poison that affects
mitochondrial respiratory chain complex III. The modes of cell death were
analyzed by time-lapse videomicroscopy, in situ end-labeling (ISEL)
technique, and ultrastructural analysis. Intracellular ATP levels were also
measured in order to detect whether the energetic stores were determinant
for the type of cell death. It was found that while apoptosis was the
prevalent cell death in the fibroblasts treated with low doses, 100 or 200
muM Antimycin A, a new type of cell demise that shared dynamic, molecular,
and morphological features with both apoptosis and necrosis represents the
most common cell death when the cells were exposed to high doses, 300 or 400
muM, of the hypoxic stimulus. This new type of cell death has been
chimerically termed aponecrosis. The inhibition of caspase 3, an enzyme
critical for the apoptotic DNA degradation, caused a clear shift from
aponecrosis to necrosis in the cell culture, suggesting that this new type
of cell death could account for an incomplete execution of the apoptotic
program and the following degeneration in necrosis. After being treated with
higher doses, i.e., 1000 muM Antimycin A, almost all of the cells died by
true necrosis. The analysis of the cellular energetic stores showed that the
levels of ATP were a primary determinant in directing toward active cell
death (apoptosis), aponecrosis, or necrosis. We conclude that chemically
induced hypoxia produces different types of cell death depending on the
intensity of the insult and on the ATP availability of the cell, and that
the classic apoptosis and necrosis may represent only two extremes of a
continuum of intermediate forms of cell demise. Copyright 2000 Wiley-Liss,

....you must realise that the difference between apoptosis and necrosis is
not so clear cut....and you will never get 100% necrosis in any one cell

Ian A. York <iayork at panix.com> wrote in message
news:814lh5$ejt$1 at panix3.panix.com...
| I thought this was going to be an easy one to find in medline, but boy was
| I wrong.
| I want to induce necrotic cell death in several lines of cultured cells.
| I want this to be all necrosis, all the time; no apoptosis sneaking in
| here.  And I want it to be a well-known protocol, so that we don't have to
| spend a lot of time justifying the system and running all the various
| controls to prove it's pure necrosis.
| But when I try to do searches, all I can find is people saying things
| like, "unlike necrotic cell death, Drug X induced apoptosis ... "
| I guess no one cares about boring old necrosis, but surely someone must
| have done a control some time.
| Any tips?
| Thanks.
| Ian
| --
|     Ian York   (iayork at panix.com)  <http://www.panix.com/~iayork/>
|     "-but as he was a York, I am rather inclined to suppose him a
|      very respectable Man." -Jane Austen, The History of England

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