Transforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling.

2.50
Hdl Handle:
http://hdl.handle.net/10541/86374
Title:
Transforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling.
Authors:
Booth, Dawn; Haley, John D; Bruskin, Arthur M; Potten, Christopher S
Abstract:
Damage to the normal replacing tissues of the body, specifically the gastro-intestinal tract, limits the treatment and hence, cure rate of cancer patients. Here, we investigate the possibility that the sensitivity of the gastro-intestinal tract can be manipulated by transforming growth factor beta3 (TGF-beta3), making it more resistant to radiation in a murine model. The effects of TGF-beta3 were assessed using the crypt microcolony assay, a test of crypt stem-cell functional competence, in animal survival studies examining diarrhoea severity, labelling index and crypt size. Prior treatment with TGF-beta3 can result in a 3- to 4-fold increase (protection factor, PF) in surviving crypts, whilst longer exposure can raise the PF to almost 12. Protection of intestinal clonogenic stem cells results in marked protection of survival with a corresponding reduction in the duration and level of diarrhoea and ultimate restoration of normal histology in surviving mice. Inhibition of proliferation can be demonstrated when sufficient TGF-beta3 exposure is studied. Crypt size is also reduced. In conclusion, TGF-beta3 protects small intestinal clonogenic stem cells from radiation damage, reducing diarrhoea and animal mortality. The mode of action is believed to be specific inhibition of stem-cell proliferation.
Affiliation:
CRC Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Transforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling. 2000, 86 (1):53-9 Int. J. Cancer
Journal:
International Journal of Cancer.
Issue Date:
1-Apr-2000
URI:
http://hdl.handle.net/10541/86374
PubMed ID:
10728594
Type:
Article
Language:
en
ISSN:
0020-7136
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBooth, Dawnen
dc.contributor.authorHaley, John Den
dc.contributor.authorBruskin, Arthur Men
dc.contributor.authorPotten, Christopher Sen
dc.date.accessioned2009-11-18T10:29:07Z-
dc.date.available2009-11-18T10:29:07Z-
dc.date.issued2000-04-01-
dc.identifier.citationTransforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling. 2000, 86 (1):53-9 Int. J. Canceren
dc.identifier.issn0020-7136-
dc.identifier.pmid10728594-
dc.identifier.urihttp://hdl.handle.net/10541/86374-
dc.description.abstractDamage to the normal replacing tissues of the body, specifically the gastro-intestinal tract, limits the treatment and hence, cure rate of cancer patients. Here, we investigate the possibility that the sensitivity of the gastro-intestinal tract can be manipulated by transforming growth factor beta3 (TGF-beta3), making it more resistant to radiation in a murine model. The effects of TGF-beta3 were assessed using the crypt microcolony assay, a test of crypt stem-cell functional competence, in animal survival studies examining diarrhoea severity, labelling index and crypt size. Prior treatment with TGF-beta3 can result in a 3- to 4-fold increase (protection factor, PF) in surviving crypts, whilst longer exposure can raise the PF to almost 12. Protection of intestinal clonogenic stem cells results in marked protection of survival with a corresponding reduction in the duration and level of diarrhoea and ultimate restoration of normal histology in surviving mice. Inhibition of proliferation can be demonstrated when sufficient TGF-beta3 exposure is studied. Crypt size is also reduced. In conclusion, TGF-beta3 protects small intestinal clonogenic stem cells from radiation damage, reducing diarrhoea and animal mortality. The mode of action is believed to be specific inhibition of stem-cell proliferation.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Cycle-
dc.subject.meshIntestine, Small-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshRadiation Injuries, Experimental-
dc.subject.meshRadiation-Protective Agents-
dc.subject.meshStem Cells-
dc.subject.meshTransforming Growth Factor beta-
dc.titleTransforming growth factor-B3 protects murine small intestinal crypt stem cells and animal survival after irradiation, possibly by reducing stem-cell cycling.en
dc.typeArticleen
dc.contributor.departmentCRC Epithelial Biology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalInternational Journal of Cancer.en
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