Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95245
Title:
Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation.
Authors:
Merritt, Anita J; Allen, Terence D; Potten, Christopher S; Hickman, John A
Abstract:
The death of small intestinal epithelial cells has been characterized and quantitated after irradiation of mice rendered homozygously null for the p53 gene. In wild-type animals homozygous for p53 a rapid (4.5 h) elevation of p53 protein was observed in the proliferative compartment of the crypts after 8 Gy of irradiation. Cells underwent cell death by apoptosis in this region. We had reported previously a total repression of apoptosis in small intestinal crypt epithelia 4.5 h after the gamma-irradiation (8 Gy) of p53 homozygously null animals. Thus, while 400 apoptotic cells were observed in 200 half crypts taken from wild-type animals at 4.5 h, this fell to background levels (10-30) in the p53 null animals (Merritt et al., 1994) and did not increase by 12 h. However, we have now found a delayed initiation of a p53-independent apoptosis after 8 Gy of gamma-radiation: at 24 h, approximately 100 apoptotic cells were observed in 200 half crypts. This late wave of apoptosis was not observed after 1 Gy of gamma-radiation. The morphological appearance of this p53-independent apoptosis suggested that death may have arisen as the result of aberrant mitosis. Analysis of the regeneration of crypts 3 days after irradiation of mice with between 11 and 17 Gy showed that there was no significant increase (P=0.135) in the potential of clonogenic cells from the p53 null animals to repopulate the crypts. The data support the idea that a p53-independent apoptotic mechanism permits the engagement of apoptosis, probably by a mitotic catastrophe, after 8 Gy of gamma-irradiation in vivo and that a loss of p53 does not make these epithelial cells radioresistant in vivo to doses of 8 Gy and above. In contrast, irradiation with 1 Gy failed to induce a p53-independent apoptosis in vivo, suggesting that the p53 'sensor' of damage was more sensitive than that engaging the p53-independent mechanism of cell death.
Affiliation:
Cancer Research Campaign Department of Epithelial Biology, Christie Hospital Trust, School of Biological Sciences, The University of Manchester, UK.
Citation:
Apoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation. 1997, 14 (23):2759-66 Oncogene
Journal:
Oncogene
Issue Date:
12-Jun-1997
URI:
http://hdl.handle.net/10541/95245
DOI:
10.1038/sj.onc.1201126
PubMed ID:
9190891
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorMerritt, Anita Jen
dc.contributor.authorAllen, Terence Den
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorHickman, John Aen
dc.date.accessioned2010-03-30T11:48:04Z-
dc.date.available2010-03-30T11:48:04Z-
dc.date.issued1997-06-12-
dc.identifier.citationApoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation. 1997, 14 (23):2759-66 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid9190891-
dc.identifier.doi10.1038/sj.onc.1201126-
dc.identifier.urihttp://hdl.handle.net/10541/95245-
dc.description.abstractThe death of small intestinal epithelial cells has been characterized and quantitated after irradiation of mice rendered homozygously null for the p53 gene. In wild-type animals homozygous for p53 a rapid (4.5 h) elevation of p53 protein was observed in the proliferative compartment of the crypts after 8 Gy of irradiation. Cells underwent cell death by apoptosis in this region. We had reported previously a total repression of apoptosis in small intestinal crypt epithelia 4.5 h after the gamma-irradiation (8 Gy) of p53 homozygously null animals. Thus, while 400 apoptotic cells were observed in 200 half crypts taken from wild-type animals at 4.5 h, this fell to background levels (10-30) in the p53 null animals (Merritt et al., 1994) and did not increase by 12 h. However, we have now found a delayed initiation of a p53-independent apoptosis after 8 Gy of gamma-radiation: at 24 h, approximately 100 apoptotic cells were observed in 200 half crypts. This late wave of apoptosis was not observed after 1 Gy of gamma-radiation. The morphological appearance of this p53-independent apoptosis suggested that death may have arisen as the result of aberrant mitosis. Analysis of the regeneration of crypts 3 days after irradiation of mice with between 11 and 17 Gy showed that there was no significant increase (P=0.135) in the potential of clonogenic cells from the p53 null animals to repopulate the crypts. The data support the idea that a p53-independent apoptotic mechanism permits the engagement of apoptosis, probably by a mitotic catastrophe, after 8 Gy of gamma-irradiation in vivo and that a loss of p53 does not make these epithelial cells radioresistant in vivo to doses of 8 Gy and above. In contrast, irradiation with 1 Gy failed to induce a p53-independent apoptosis in vivo, suggesting that the p53 'sensor' of damage was more sensitive than that engaging the p53-independent mechanism of cell death.en
dc.language.isoenen
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshClone Cells-
dc.subject.meshDNA Replication-
dc.subject.meshG2 Phase-
dc.subject.meshGamma Rays-
dc.subject.meshIntestinal Mucosa-
dc.subject.meshIntestine, Small-
dc.subject.meshMice-
dc.subject.meshMicroscopy, Electron-
dc.subject.meshMitosis-
dc.subject.meshMitotic Index-
dc.subject.meshTumor Suppressor Protein p53-
dc.titleApoptosis in small intestinal epithelial from p53-null mice: evidence for a delayed, p53-independent G2/M-associated cell death after gamma-irradiation.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Epithelial Biology, Christie Hospital Trust, School of Biological Sciences, The University of Manchester, UK.en
dc.identifier.journalOncogeneen
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