Online citations, reference lists, and bibliographies.
← Back to Search

Identification Of Programmed Cell Death In Situ Via Specific Labeling Of Nuclear DNA Fragmentation

Y. Gavrieli, Y. Sherman, S. Ben-Sasson
Published 1992 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
Programmed cell death (PCD) plays a key role in developmental biology and in maintenance of the steady state in continuously renewing tissues. Currently, its existence is inferred mainly from gel electrophoresis of a pooled DNA extract as PCD was shown to be associated with DNA fragmentation. Based on this observation, we describe here the development of a method for the in situ visualization of PCD at the single-cell level, while preserving tissue architecture. Conventional histological sections, pretreated with protease, were nick end labeled with biotinylated poly dU, introduced by terminal deoxy- transferase, and then stained using avidin-conjugated peroxidase. The reaction is specific, only nuclei located at positions where PCD is expected are stained. The initial screening includes: small and large intestine, epidermis, lymphoid tissues, ovary, and other organs. A detailed analysis revealed that the process is initiated at the nuclear periphery, it is relatively short (1-3 h from initiation to cell elimination) and that PCD appears in tissues in clusters. The extent of tissue-PCD revealed by this method is considerably greater than apoptosis detected by nuclear morphology, and thus opens the way for a variety of studies.
This paper references
10.1016/0167-5699(90)90048-E
Cellular signalling in programmed cell death (apoptosis).
D. McConkey (1990)
10.1016/0092-8674(91)90536-8
A polyadenylate binding protein localized to the granules of cytolytic lymphocytes induces DNA fragmentation in target cells
Q. Tian (1991)
Cellular signalling in programmed cell death ( apopteais ) . lmmunol
S. Orrenius (1990)
10.1038/284555A0
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
A. Wyllie (1980)
M i c t ~ and electron microscopic analysis of target cell lysis induced by cTtotoxic T lymphocytes, lmmuno/ogy
A. Mater (1979)
10.1073/PNAS.74.12.5579
DNA degradation in terminally differentiating lens fiber cells from chick embryos.
D. W. Appleby (1977)
Hepatocyte life history. L/ver
H. liver (1991)
A Pathologist's View of Cell Death
W J Hun (1987)
Cytolysis induced by human lymphotoxin.
S. W. Russell (1972)
programmed cell death (apopteais). lmmunol
S. P. Modak (1972)
Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death.
J. Cohen (1984)
CTL: virus control cells first and cytolytic cells seomad? lreammo
E. Martz (1989)
Mict~ and electron microscopic analysis of target cell lysis induced by cTtotoxic T lymphocytes, lmmuno/ogy
A Mater (1979)
Apoptosis. In Perspectives on Mammalian Cell Death. C. S. Potten
J F R Kerr (1987)
10.1016/0003-9861(89)90119-7
Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration.
D. McConkey (1989)
Topoisomerase II-reactive chemotherapeutic drugs induce apoptosis in thymocytes.
P. Walker (1991)
10.1016/0092-8674(91)90002-G
Programmed cell death: Apoptosis and oncogenesis
G. Williams (1991)
DNA degradation in terminally differentiating
D. W. Appleby (1977)
10.1016/0167-5699(90)90047-D
Death and transfiguration of cortical thymocytes: a reconsideration.
E. Rothenberg (1990)
Death by suicide: one way to go in mammalian cellular development?
D. Ucker (1991)
10.1002/EJI.1830200411
CD4+CD8+ thymocytes are susceptible to DNA fragmentation induced by phorbol ester, calcium ionophore and anti‐CD3 antibody
T. Tadakuma (1990)
10.1007/978-94-011-6921-9_2
Cell death: a new classification separating apoptosis from necrosis
A. Wyllie (1981)
Apoptosis
J.F.R. Kerr (1987)
Apoptosis is associated with the exten
B. Motyka (1991)
The streaming liver H. Hepatocyte life history. L/ver
N Arber (1988)
CD 4 + CD 8 + thymocytes are susceptible to DNA fragmentation induced by phorbolester , calcium ionophore and anti - CD 3 antibody
M. Streuti (1990)
Mutations affecting pmgmnmied ce
E. M. Hedgecock (1983)
10.1016/0167-5699(89)90231-4
CTL: virus control cells first and cytolytic cells second? DNA fragmentation, apoptosis and the prelytic halt hypothesis.
E. Martz (1989)
10.1095/BIOLREPROD38.5.1181
Size-frequency analysis of atresia in cycling rats.
A. Hirshfield (1988)
CTL : virus control cells first and cytolytic cells seomad ? lreammo / . Today
C. S. Potten (1989)
10.1002/EJI.1830210825
Apoptosis is associated with the extensive B cell death in the sheep ileal Peyer's patch and the chicken bursa of Fabricius: A possible role in B cell selection
B. Motyka (1991)
Mutations affecting pmgmnmied ce , ll deaths in the nematode C elegana
A. N. Hirshfleld (1988)
10.1016/0014-4827(91)90380-D
Spermine prevents endonuclease activation and apoptosis in thymocytes.
B. Brüne (1991)
M i c t ~ and electron microscopic analysis of target cell lysis induced by cTtotoxic T lymphocytes , lmmuno
A. Mater (1979)
10.1098/rspb.1976.0011
The mechanism of T cell mediated cytotoxicity II. morphological studies of cell death by time-lapse microcinematography
C. Sanderson (1976)
Activation-induced cell death in T cell hybridomas is due to apoptosis. Morphologic aspects and DNA fragmentation.
Y. Shi (1990)
The mechanism ofT cell mediated cytotoxicity II
C. J. Sanderson (1976)
Mutations affecting pmgmnmied ce, ll deaths in the nematode C elegana
E M Hedgecock (1983)
10.1038/bjc.1972.33
Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics
J. Kerr (1972)
Situ Visualization of Programmed Cell Death
Gavrieli
10.1016/0014-4827(72)90434-X
Detection and measurement of single-strand breaks in nuclear DNA in fixed lens sections.
S. Modak (1972)
10.1111/J.1600-0676.1988.TB00972.X
The streaming liver. II. Hepatocyte life history.
N. Arber (1988)
10.1002/PATH.1711420112
Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis
A. Wyllie (1984)
10.1111/1523-1747.EP12478519
Programmed cell death in terminally differentiating keratinocytes: role of endogenous endonuclease.
C. McCall (1991)
The biology of epithelial cell populations
N. A. Wright (1984)
10.1139/O90-160
The biochemistry of cell death by apoptosis.
W. Bursch (1990)
10.1073/PNAS.80.20.6361
Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis.
R. C. Duke (1983)
Ultrastructural asla~ts of cell death
T. D. Allen (1987)
Calcium activated DNA fragmentation
D. J. MeConkey (1989)
10.1016/0012-1606(88)90322-3
Immunocytochemical localization of transient DNA strand breaks in differentiating myotubes using in situ nick-translation.
B. A. Dawson (1988)
10.1016/S0074-7696(08)62312-8
Cell death: the significance of apoptosis.
A. Wyllie (1980)
10.1016/0022-5193(82)90360-5
The genetic program of cell death. Hypothesis and some applications: transformation, carcinogenesis, ageing.
S. Umansky (1982)
reconsideration, lmmunol. Today
W S. (1972)
10.1096/fasebj.3.7.2497041
Calcium‐activated DNA fragmentation kills immature thymocytes
D. McConkey (1989)
10.1016/0022-1759(91)90198-O
A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.
I. Nicoletti (1991)



This paper is referenced by
10.1016/j.vetimm.2014.01.004
Bcl-2/caspase 3 mucosal imbalance favors T cell resistance to apoptosis in dogs with inflammatory bowel disease.
A. Jergens (2014)
10.1007/978-3-7091-6842-4
Advances in Research on Neurodegeneration
P. (1997)
10.1007/BF00315834
Antibody against single-stranded DNA detects both programmed cell death and drug-induced apoptosis
I. Naruse (2004)
10.1016/0959-4388(93)90156-S
Strategies for rescue of retinal photoreceptor cells
A. Milam (1993)
10.1111/j.1440-1827.2004.01611.x
Prognostic value of apoptosis and apoptosis‐associated proteins in salivary gland adenoid cystic carcinoma
L. Jia (2004)
10.1111/j.1440-1827.1995.tb03511.x
Minigemistocytic astrocytoma with frequent apoptoses: Analysis of tumor growth
Y. Higami (1995)
10.1046/j.1440-1827.2000.01025.x
Quantitative analysis of apoptotic cell death in granulomatous inflammation induced by intravenous challenge with Cryptococcus neoformans and bacillus Calmette‐Guérin vaccine
K. Matsunaga (2000)
10.1002/tox.20688
Necrosis and apoptosis of renal tubular epithelial cells in rats exposed to 3‐methyl‐4‐nitrophenol
Z. Yue (2012)
10.1002/mrd.21374
Age‐related instability in spermatogenic cell nuclear and mitochondrial DNA obtained from Apex1 heterozygous mice
K. Vogel (2011)
Molecular mechanisms of cell death and regeneration following ischaemic renal injury
A. Lewington (2003)
A transgenic mouse with PMP-22 directed GFP expression : a model for Schwann cell behaviour
A. M. Wright (2001)
10.5445/IR/1000099430
Pulsed electric field (PEF)-assisted protein recovery from microalgae biomass for food and feed applications
D. Scherer (2018)
10.1111/1523-1747.EP12413590
Abnormal Bcl-2 and "tissue" transglutaminase expression in psoriatic skin.
L. Bianchi (1994)
10.1136/bjo.79.2.186
Cell loss in retinal dystrophies by apoptosis--death by informed consent!
Cheryl Y. Gregory (1995)
Apoptosis in Pam212, an epidermal keratinocyte cell line: a possible role for bcl-2 in epidermal differentiation.
J. Marthinuss (1995)
10.1084/JEM.181.4.1557
Novel packages of viral and self-antigens are generated during apoptosis
A. Rosen (1995)
10.1016/0006-8993(95)00145-G
DNA fragmentation indicative of apoptosis following unilateral cerebral hypoxia-ischemia in the neonatal rat
I. Hill (1995)
10.1016/0896-6273(95)90314-3
Defective glia induce neuronal apoptosis in the repo visual system of Drosophila
W. Xiong (1995)
10.1016/0006-8993(94)01448-Q
Olfactory experience modulates apoptosis in the developing olfactory bulb
J. Najbauer (1995)
10.1016/0022-3468(95)90752-1
Bcl-2 oncoprotein expression and apoptosis in neuroblastoma.
H. Ikeda (1995)
10.1007/978-3-642-61180-3_13
Molecular Mechanisms Controlling Susceptibitliy to Tumor Necrosis Factor Induced Cell Death
J. Klefström (1996)
10.1002/CNE.903630209
In situ labeling of apoptotic cell death in the cerebral cortex and thalamus of rats during development
R. Spreafico (1995)
10.1007/BF02284800
Apoptotic cell death of photoreceptor cells in mice deficient for the adhesion molecule on glia (AMOG, the β2-subunit of the Na,K-ATPase)
M. Molthagen (1996)
Curable and noncurable paediatric cancer malignancies: lessons from
A. Toren (1996)
10.14748/BMR.V4.196
Apoptosis in neurodegenerative diseases: to be or not to be?
H.J.L.M. Timmers (1995)
10.1182/BLOOD.V87.6.2450.BLOODJOURNAL8762450
Activation-dependent alpha5beta1 integrin-mediated adhesion to fibronectin decreases proliferation of chronic myelogenous leukemia progenitors and K562 cells.
B. Lundell (1996)
10.1074/JBC.271.7.3667
Induction of Apoptosis by Pyrrolidinedithiocarbamate and N-Acetylcysteine in Vascular Smooth Muscle Cells (*)
J. Tsai (1996)
10.11182/JASTRO1989.8.63
DETECTION OF DNA FRAGMENTATION IN γ-IRRADIATED RAT TONGUE EPITHEIUM
M. Yasuda (1996)
10.1182/BLOOD.V87.6.2244.BLOODJOURNAL8762244
The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques.
N. Philpott (1996)
10.1002/(SICI)1097-0320(19960601)24:2<131::AID-CYTO5>3.0.CO;2-M
A novel assay to measure loss of plasma membrane asymmetry during apoptosis of adherent cells in culture.
M. van Engeland (1996)
10.2108/zsj.13.559
Germ Cell Death in the Degenerating Right Ovary of the Chick Embryo
A. Ukeshima (1996)
10.1016/0306-4522(96)00148-0
Anatomical studies of DNA fragmentation in rat brain after systemic kainate administration
S. Weiss (1996)
See more
Semantic Scholar Logo Some data provided by SemanticScholar