The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
TUNEL Apoptotic Cell Detection in Tissue Sections: Critical Evaluation and Improvement
Abstract
TUNEL, i.e., terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling, has become a widely used staining method to assist in detection of apoptotic cells in tissue sections. However, despite its apparent simplicity, this technique has led to considerable disappointment because of its serious limitations in sensitivity and, even more, in specificity. We reviewed the limitations and artifacts of TUNEL and designed a comprehensive protocol to reassess the various procedures in use for five crosslinking and/or precipitating fixatives. By introducing microwave heating in extreme pH-value solutions (pH 3 for formalin and pH 10.6 for Bouin's fixative) coupled with proteolysis, we obtained an intense staining of 70–80% of apoptotic cells and bodies on archival tissue blocks, with little or no background. Owing to the enhanced sensitivity, early stages of apoptosis could be visualized and may enlarge our vision of the apoptotic cell beyond the mere image of shrinkage necrosis. We conclude that TUNEL remains a technique as useful as it is delicate, requiring critical interpretation of the staining. This study points out that, on archival tissues, despite the technical improvements we propose no protocol can be the final answer to all problems. Technique must be readjusted for any variation in tissue processing. However, step-by-step progress has rendered this method not only applicable but also performable within the constraints of archival surgical pathology specimens.
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Cites
Apoptosis: A Basic Biological Phenomenon with Wideranging Implications in Tissue Kinetics
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972) · British Journal of Cancer · doi:10.1038/bjc.1972.33 · Cited by 15,725
Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.
Gavrieli, Y., Sherman, Y., & Ben-Sasson, S. A. (1992) · The Journal of cell biology · doi:10.1083/jcb.119.3.493 · Cited by 9,444
Cell Death: The Significance of Apoptosis
Wyllie, A. H., Kerr, J. F. R., & Currie, A. R. (1980) · International Review of Cytology · doi:10.1016/s0074-7696(08)62312-8 · Cited by 7,162
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
Wyllie, A. H. (1980) · Nature · doi:10.1038/284555a0 · Cited by 4,504
Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells
Ostling, O., & Johanson, K. J. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(84)90411-x · Cited by 1,694
Chen, Y., & Wu, H. (2010) · Chinese Science Bulletin · doi:10.1007/s11434-010-3275-4 · Cited by 1,594
Kraupp, B. G., Ruttkay-Nedecky, B., Koudelka, H., Bukowska, K., Bursch, W., & Schulte-Hermann, R. (1995) · Hepatology · doi:10.1002/hep.1840210534 · Cited by 1,156
Gorczyca, W., GONG, J., & Darżynkiewicz, Z. (1993) · PubMed · Cited by 982
A new method to detect apoptosis in paraffin sections: in situ end-labeling of fragmented DNA.
Wijsman, J. H., Jonker, R. R., Keijzer, R., van de Velde, C. J., Cornelisse, C. J., & van Dierendonck, J. H. (1993) · Journal of Histochemistry & Cytochemistry · doi:10.1177/41.1.7678025 · Cited by 802
Gold, R., Schmied, M. C., Giegerich, G., Breitschopf, H., Hartung, H., Toyka, K. V., & Lassmann, H. (1994) · PubMed · Cited by 675
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Molecular and cellular mechanisms of the anabolic effect of intermittent PTH
Jilka, R. L. (2007) · Bone · doi:10.1016/j.bone.2007.03.017 · Cited by 720
Fridman, G., Shereshevsky, A., Jost, M. M., Brooks, A. D., Fridman, A., Gutsol, A., Vasilets, V., & Friedman, G. (2007) · Plasma Chemistry and Plasma Processing · doi:10.1007/s11090-007-9048-4 · Cited by 594
Apoptosis and necroptosis in the liver: a matter of life and death
Schwabe, R. F., & Luedde, T. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0065-y · Cited by 582
Behavioral and Anatomical Correlates of Chronic Episodic Hypoxia during Sleep in the Rat
Gozal, D., Daniel, J. M., & Dohanich, G. P. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-07-02442.2001 · Cited by 577
Apoptosis Has a Prolonged Role in the Neurodegeneration after Hypoxic Ischemia in the Newborn Rat
Nakajima, W., Ishida, A., Lange, M. S., Gabrielson, K. L., Wilson, M. A., Martin, L. J., Blue, M. E., & Johnston, M. V. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-21-07994.2000 · Cited by 422
Metadata
- Authors
- Labat-Moleur, F., Guillermet, C., Lorimier, P., Robert, C., Lantuejoul, S., Brambilla, E., & Negoescu, A.
- Venue
- Journal of Histochemistry & Cytochemistry
- Publisher
- SAGE Publications
- Published
- 1998-03
- Volume
- 46
- Issue
- 3
- Pages
- 327-334
- ISSN
- 0022-1554 (ISSN-L)
- 1551-5044
- OpenAlex
- W2162385486
- Cited by
- 351
- References
- 25
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- closed
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- Labat-Moleur, F., Guillermet, C., Lorimier, P., Robert, C., Lantuejoul, S., Brambilla, E., & Negoescu, A. (1998). TUNEL Apoptotic Cell Detection in Tissue Sections: Critical Evaluation and Improvement. Journal of Histochemistry & Cytochemistry. https://doi.org/10.1177/002215549804600306
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