Drug-induced necrosis

Nick Theodorakis nicholas_theodorakis at urmc.rochester.edu
Sat Nov 20 23:05:07 EST 1999


In article <817ntf$obn$1 at panix3.panix.com>, iayork at panix.com (Ian A.
York) wrote:
> In article <383780C0.C63DD8 at home.com>, Menoret  <menoret at home.com>
> wrote:
> >Well, I think you are probably right. For me necrosis without any
> trace
> >of apoptosis has to be a violent phenomenon, like immediate tissue
> >destruction. Most of the so-called necrosis observed in vivo
> looks like
> >different kind of post apoptotic cell death. What is your
> definition of
> >necrosis ? Are you talking of a cell or of a tissue ?
> We're definitely talking about cells, as in cultured cells.  The
> definition of necrosis (if there is one) seems to be a negative
> one--cell
> death that isn't apoptosis.  Of course, apoptosis used to be
> defined as
> cell death that isn't necrosis, but I think the concept of
> apoptosis is
> more based on molecular events now.
> I don't really know what necrosis is at the single-cell level.  I
> think
> of things like reactive oxygen species or anoxia, for most cells,
> leading
> to a violent cell death, but one that takes several hours to
> occur--not as
> simple as being torn from limb to limb.  The lack of a good
> definition is
> probably one of the problems we're facing in this question.
> 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

Ian, I think you've come to the crux of the problem here. Necrosis
isn't a process, it just means something died, and it did it in boring
way. I don't think anybody ever thought about it as a process until
apoptosis became "popular," at which point people considered it as an
"alternative" to death by apoptosis. I would be surprised if you can
come up with a unifying set of criteria that says: "the features of
necrotic cell death are, yada yada yada."

I also think part of the problem might be that when a cell is in
trouble, it would probably at least _try_ to undergo apoptosis, but if
it is too sick it might die before it has a chance to kill itself.

Having said that, let me try to think of some things that might work
off the top of my head:

Complement? Or something else that might poke a hole in the membrane?

Does azide trigger apoptosis? If not, that might work.

Severe hyperthermia? Like maybe 45C or more?

Infection with a lytic virus like Adeno?

Nick



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