PMID- 33260475
OWN - NLM
STAT- MEDLINE
DCOM- 20210305
LR  - 20210305
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 23
DP  - 2020 Nov 29
TI  - Do TUNEL and Other Apoptosis Assays Detect Cell Death in Preclinical Studies?
LID - 10.3390/ijms21239090 [doi]
LID - 9090
AB  - The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      assay detects DNA breakage by labeling the free 3'-hydroxyl termini. Given that 
      genomic DNA breaks arise during early and late stages of apoptosis, TUNEL 
      staining continues to be widely used as a measure of apoptotic cell death. The 
      advantages of the assay include its relative ease of performance and the broad 
      availability of TUNEL assay kits for various applications, such as single-cell 
      analysis of apoptosis in cell cultures and tissue samples. However, as briefly 
      discussed herein, aside from some concerns relating to the specificity of the 
      TUNEL assay itself, it was demonstrated some twenty years ago that the early 
      stages of apoptosis, detected by TUNEL, can be reversed. More recently, 
      compelling evidence from different biological systems has revealed that cells can 
      recover from even late stage apoptosis through a process called anastasis. 
      Specifically, such recovery has been observed in cells exhibiting caspase 
      activation, genomic DNA breakage, phosphatidylserine externalization, and 
      formation of apoptotic bodies. Furthermore, there is solid evidence demonstrating 
      that apoptotic cells can promote neighboring tumor cell repopulation (e.g., 
      through caspase-3-mediated secretion of prostaglandin E(2)) and confer resistance 
      to anticancer therapy. Accordingly, caution should be exercised in the 
      interpretation of results obtained by the TUNEL and other apoptosis assays (e.g., 
      caspase activation) in terms of apoptotic cell demise.
FAU - Mirzayans, Razmik
AU  - Mirzayans R
AD  - Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, 
      AB T6G 1Z2, Canada.
FAU - Murray, David
AU  - Murray D
AD  - Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, 
      AB T6G 1Z2, Canada.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20201129
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Antineoplastic Agents)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/pharmacology/therapeutic use
MH  - *Apoptosis/drug effects
MH  - *Biological Assay
MH  - DNA Breaks
MH  - Humans
MH  - *In Situ Nick-End Labeling
MH  - Neoplasms/drug therapy/pathology
PMC - PMC7730366
OTO - NOTNLM
OT  - DNA strand breakage
OT  - TUNEL
OT  - anastasis
OT  - apoptosis
OT  - cancer therapy
OT  - micronucleation
OT  - polyploid giant cancer cells
OT  - reversal
OT  - senescence
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/03 06:00
MHDA- 2021/03/06 06:00
PMCR- 2020/12/01
CRDT- 2020/12/02 01:01
PHST- 2020/11/12 00:00 [received]
PHST- 2020/11/26 00:00 [revised]
PHST- 2020/11/26 00:00 [accepted]
PHST- 2020/12/02 01:01 [entrez]
PHST- 2020/12/03 06:00 [pubmed]
PHST- 2021/03/06 06:00 [medline]
PHST- 2020/12/01 00:00 [pmc-release]
AID - ijms21239090 [pii]
AID - ijms-21-09090 [pii]
AID - 10.3390/ijms21239090 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Nov 29;21(23):9090. doi: 10.3390/ijms21239090.