On Thu, 30 Oct 1997 LAADAMS@am.pnu.com wrote:
> This is a basic science question. Does anyone have a definition of oncosis
> which differentiates this method of cell death from apoptosis, including
> morphological and/or biochemical hallmarks? I have been treating HT29
> (human colon adenocarcinoma) cells with a potential antitumor drug and I
> don't think this agent is killing the cells by apoptosis. Others in my
> group do not agree. The cells start to swell after 24-48 hours of
> treatment and by 96 hours the most of the culture is dead. At no point in
> the time course do the cells demonstrate true positive TUNEL results. I
> have only looked at DNA laddering once and got ambiguous results, i.e., I
> think I looked at too late of a time point.
Well, here's one of those instances where internet does double-good duty.
I just walked in from tonight's AFIP Stowell lecture by Ben Trump (Chair,
Pathology, Univ Maryland) where he spent an hour on fascinating details of
this topic that his group has advanced very much. The recently educated
simple fool's answer (mine) is that oncosis is a cellular response to
injury characterized first by swelling (onco, Greek, "swelling or mass"),
while apoptosis (Greek, "falling off") is characterized first by blebbing
and fragmentation accompanying an initial *decrease* in cell volume. The
cell chemistries for the two paths are diagrammed as related but distinct
in ways I don't trust myself to remember. Luckily, I don't have to. A
quick medline search gives the following abstract:
-------------------------------------------------------------------------------
TITLE: The pathways of cell death: oncosis, apoptosis, and
necrosis.
AUTHOR: Trump BF; Berezesky IK; Chang SH; Phelps PC
AUTHOR Department of Pathology, University of Maryland School of
AFFILIATION: Medicine, Baltimore 21201, USA.
SOURCE: Toxicol Pathol 1997 Jan-Feb;25(1):82-8
NLM CIT. ID: 97215504
ABSTRACT: The pathways and identification of cell injury and cell
death are of key importance to the practice of diagnostic
and research toxicologic pathology. Following a lethal
injury, cellular reactions are initially reversible.
Currently, we recognize two patterns, oncosis and apoptosis.
Oncosis, derived from the Greek word "swelling," is the
common pattern of change in infarcts and in zonal killing
following chemical toxicity, e.g., centrilobular hepatic
necrosis after CC14 toxicity. In this common reaction, the
earliest changes involve cytoplasmic blebbing, dilatation of
the endoplasmic reticulum (ER), swelling of the cytosol,
normal or condensed mitochondria, and chromatin clumping in
the nucleus. In apoptosis, the early changes involve cell
shrinkage, cytosolic shrinkage, more marked chromatin
clumping, cytoplasmic blebbing, swollen ER on occasion, and
mitochondria that are normal or condensed. Following cell
death, both types undergo postmortem changes collectively
termed "necrosis." In the case of oncosis, this typically
involves broad zones of cells while, in the case of
apoptosis, the cells and/or the fragments are often
phagocytized prior to their death by adjacent macrophages or
parenchymal cells. In either case, the changes converge to a
pattern that involves mitochondrial swelling, mitochondrial
flocculent densities and/or calcification, karyolysis, and
disruption of plasmalemmal continuity. The biochemical
mechanisms of cell death are currently under intense study,
particularly concerning the genes involved in the process.
Pro-death genes include p53, the ced-3/ICE proteases, and
the Bax family. Anti-death genes include ced-9/Bcl-2 and the
adenovirus protein EIB. It is clear that ion deregulation,
particularly that of [Ca2+]i plays an important role in cell
death following either apoptosis or oncosis. Genetic
evidence strongly indicates that activation of proteases is
an important step, possibly very near to the point where
cell death occurs.
MAIN MESH Apoptosis/*DRUG EFFECTS
SUBJECTS: Neoplasms, Experimental/*CHEMICALLY INDUCED/*PATHOLOGY
ADDITIONAL Animal
MESH SUBJECTS: Cell Death/DRUG EFFECTS
Necrosis
Support, U.S. Gov't, Non-P.H.S. Support, U.S. Gov't, P.H.S.
PUBLICATION JOURNAL ARTICLE
TYPES: REVIEW
REVIEW, TUTORIAL
LANGUAGE: Eng
------------------------------------------------------------------------------
I'll bet this ref will get you started on the biochemical distinctions, as
well as the morphological ones. There's a bushel more of stuff, much in
the pharmacology literature, some on-line full text through PubMed.
Robert L. Becker, Jr.
Col, USAF, MC
Department of Cellular Pathology
Armed Forces Institute of Pathology
Washington, DC 20306-6000
202-782-1573
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