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
Cytolysis induced by human lymphotoxin.
S. W. Russell (1972)
Hepatocyte life history. L/ver
H. liver (1991)
10.1038/284555A0
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
A. Wyllie (1980)
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)
A Pathologist's View of Cell Death
W J Hun (1987)
Cellular signalling in programmed cell death ( apopteais ) . lmmunol
S. Orrenius (1990)
10.1016/0167-5699(90)90048-E
Cellular signalling in programmed cell death (apoptosis).
D. McConkey (1990)
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)
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)
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)
CTL : virus control cells first and cytolytic cells seomad ? lreammo / . Today
C. S. Potten (1989)
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
10.1111/1523-1747.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)
10.1002/EJI.1830200411
CD4+CD8+ thymocytes are susceptible to DNA fragmentation induced by phorbol ester, calcium ionophore and anti‐CD3 antibody
T. Tadakuma (1990)
10.1016/0167-5699(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/PATH.1711420112
Chromatin cleavage in apoptosis: Association with condensed chromatin morphology and dependence on macromolecular synthesis
A. Wyllie (1984)
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)
10.1016/0014-4827(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)
Mutations affecting pmgmnmied ce , ll deaths in the nematode C elegana
A. N. Hirshfleld (1988)
CTL: virus control cells first and cytolytic cells seomad? lreammo
E. Martz (1989)
Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death.
J. Cohen (1984)
programmed cell death (apopteais). lmmunol
S. P. Modak (1972)
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)
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)
reconsideration, lmmunol. Today
W S. (1972)
10.1096/fasebj.3.7.2497041
Calcium‐activated DNA fragmentation kills immature thymocytes
D. McConkey (1989)
10.1016/0022-5193(82)90360-5
The genetic program of cell death. Hypothesis and some applications: transformation, carcinogenesis, ageing.
S. Umansky (1982)
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)
10.1016/0003-9861(89)90119-7
Glucocorticoids activate a suicide process in thymocytes through an elevation of cytosolic Ca2+ concentration.
D. McConkey (1989)
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)
10.1098/rspb.1976.0011
The mechanism of T cell mediated cytotoxicity II. morphological studies of cell death by time-lapse microcinematography
C. Sanderson (1976)
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)
10.1073/PNAS.80.20.6361
Endogenous endonuclease-induced DNA fragmentation: an early event in cell-mediated cytolysis.
R. C. Duke (1983)
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)



This paper is referenced by
10.1002/EJI.1830240608
Transforming growth factor‐β2 induces apoptosis of murine T cell clones without down‐regulating bcl‐2 mRNA expression
M. Weller (1994)
10.1002/(SICI)1097-0029(19981101)43:3<233::AID-JEMT5>3.0.CO;2-L
H‐7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells
Al‐Hassan Shabana (1998)
10.1016/S0012-1606(03)00241-0
Arrested apoptosis of nurse cells during Hydra oogenesis and embryogenesis.
U. Technau (2003)
Response of Day 8 Equine Embryos to Saccharide Solutions at Various Temperatures
B. Foster (2012)
10.1084/JEM.184.4.1513
Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain
P. Dowling (1996)
10.1002/mc.20305
A plant lignan, 3′‐O‐Methyl‐Nordihydroguaiaretic acid, suppresses papillomavirus E6 protein function, stabilizes p53 protein, and induces apoptosis in cervical tumor cells
K. Allen (2007)
10.1101/SQB.1994.059.01.050
Tumorigenic and developmental effects of combined germ-line mutations in Rb and p53.
B. Williams (1994)
10.1002/pros.21019
Comparison of ACINUS, caspase‐3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis
S. S. Singh (2009)
uveitis in the Fischer 344 rat Apoptosis is a prominent feature of acute anterior
J. Smith (2000)
10.1002/(SICI)1097-0045(19980515)35:3<193::AID-PROS5>3.0.CO;2-I
Three‐dimensional ultrastructure of apoptotic nuclei in rat prostatic epithelial cells revealed by a quick‐freezing and deep‐etching method
M. Kubo (1998)
10.1007/BF00171377
Cell death and disposal in retinoblastoma: an electron microscopic study
Ernst R. Büchi (2004)
Induction of Apoptosis by Human Nbk / Bik , a BH 3-Containing Protein That Interacts with E 1 B 19 K
Jeonghoon Han (1996)
10.1007/978-3-662-03122-3_1
Hormonal Control of Prostatic Differentiation and Morphogenesis: The Impact of Apoptosis and Steroid Hormone Receptor Expression
G. Aumüller (1995)
10.1016/0959-8049(95)00006-5
Proliferation and apoptosis in neuroblastoma: subdividing the mitosis-karyorrhexis index.
C. Gestblom (1995)
10.1007/978-3-642-79414-8_10
A new function for an old enzyme: the role of DNase I in apoptosis.
H. Mannherz (1995)
10.1002/(SICI)1097-4598(199706)20:6<702::AID-MUS7>3.0.CO;2-C
Expression of Fas antigen is not associated with apoptosis in human myopathies
A. Inukai (1997)
Multiple apoptotic death types triggered through activation of separate pathways by cAMP and inhibitors of protein phosphatases in one (IPC leukemia) cell line.
B. Gjertsen (1994)
10.1002/(SICI)1096-9896(199905)188:1<100::AID-PATH306>3.0.CO;2-O
Changes in elemental concentrations are associated with early stages of apoptosis in human monocyte–macrophages exposed to oxidized low‐density lipoprotein: an X‐ray microanalytical study
J. Skepper (1999)
2 Neural Stem Cells
P. Taupin (2005)
10.1002/(SICI)1521-4141(199805)28:05<1554::AID-IMMU1554>3.0.CO;2-N
CD28 co‐stimulation is intact and contributes to prolonged ex vivo survival of hyporesponsive synovial fluid T cells in rheumatoid arthritis
M. Maurice (1998)
Pokazatelji oštećenja i oporavka u različitim moždanim regijama i vremenskim intervalima nakon traumatske ozljede mozga u štakora
Dolenec Petra (2017)
10.1002/(SICI)1096-9896(199610)180:2<152::AID-PATH649>3.0.CO;2-Y
APOPTOSIS OF CRYPT EPITHELIAL CELLS IN ULCERATIVE COLITIS
M. Iwamoto (1996)
10.1046/j.1440-1827.2003.01476.x
Proliferation kinetics and apoptosis of serrated adenoma of the colorectum
Koji Komori (2003)
10.1111/j.1440-1827.1995.tb03388.x
Cell death in colorectal polyps as evaluated by in situ 3‘‐tailing reaction and its relationship to BCL‐2 expression
T. Nakamura (1995)
10.1046/j.1524-475x.2001.00501.x
Detection of apoptosis in keloids and a comparative study on apoptosis between keloids, hypertrophic scars, normal healed flat scars, and dermatofibroma
Y. Akasaka (2001)
10.1111/j.1749-6632.1999.tb07922.x
Apoptosis‐related Functional Features of the DNaseI‐like Family of Nucleases
Q. Liu (1999)
10.1007/s00427-004-0456-7
Apoptotic wing degeneration and formation of an altruism-regulating glandular appendage (gemma) in the ponerine ant Diacamma sp. from Japan (Hymenoptera, Formicidae, Ponerinae)
A. Gotoh (2004)
10.1111/j.1750-3639.1995.tb00605.x
Programmed Cell Death in the Dysmyelinating Mutants
R. Skoff (1995)
10.1016/0165-0173(95)00003-L
The role of inducible transcription factors in apoptotic nerve cell death
M. Dragunow (1995)
10.1038/377552A0
Radiation-induced cell cycle arrest compromised by p21 deficiency
J. Brugarolas (1995)
10.1016/0378-5955(95)00109-H
Base-to-apex gradient of cell proliferation in the chick cochlea following kanamycin-induced hair cell loss
E. Hashino (1995)
10.1007/BF00417859
Apoptosis in lactating and involuting mouse mammary tissue demonstrated by nick-end DNA labelling
L. Quarrie (2004)
See more
Semantic Scholar Logo Some data provided by SemanticScholar