Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95178
Title:
Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
Authors:
Potten, Christopher S; Booth, Dawn; Haley, J D
Abstract:
The gastrointestinal tract, with its rapid cell replacement, is sensitive to cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy. Here, we have investigated the use of one growth modulator to manipulate the cell cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a known inhibitor of cell cycle progression through G1, was used to alter intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation, which was used as a model cytotoxic agent. Using a crypt microcolony assay as a measure of functional competence of gastrointestinal stem cells, it was shown that the administration of TGF-beta3 over a 24-h period before irradiation increased the number of surviving crypts by four- to six-fold. To test whether changes in crypt survival are reflected in the well-being of the animal, survival time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals survived within a period of about 12 days, while prior treatment with TGF-beta3 provided significant protection against this early gastrointestinal animal death, with 95% of the treated animals surviving for greater than 30 days.
Affiliation:
Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Citation:
Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. 1997, 75 (10):1454-9 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
1997
URI:
http://hdl.handle.net/10541/95178
PubMed ID:
9166937
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorBooth, Dawnen
dc.contributor.authorHaley, J Den
dc.date.accessioned2010-03-29T14:09:25Z-
dc.date.available2010-03-29T14:09:25Z-
dc.date.issued1997-
dc.identifier.citationPretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. 1997, 75 (10):1454-9 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid9166937-
dc.identifier.urihttp://hdl.handle.net/10541/95178-
dc.description.abstractThe gastrointestinal tract, with its rapid cell replacement, is sensitive to cytotoxic damage and can be a site of dose-limiting toxicity in cancer therapy. Here, we have investigated the use of one growth modulator to manipulate the cell cycle status of gastrointestinal stem cells before cytotoxic exposure to minimize damage to this normal tissue. Transforming growth factor beta-3 (TGF-beta3), a known inhibitor of cell cycle progression through G1, was used to alter intestinal crypt stem cell sensitivity before 12-16 Gy of gamma irradiation, which was used as a model cytotoxic agent. Using a crypt microcolony assay as a measure of functional competence of gastrointestinal stem cells, it was shown that the administration of TGF-beta3 over a 24-h period before irradiation increased the number of surviving crypts by four- to six-fold. To test whether changes in crypt survival are reflected in the well-being of the animal, survival time analyses were performed. After 14.5 Gy of radiation, only 35% of the animals survived within a period of about 12 days, while prior treatment with TGF-beta3 provided significant protection against this early gastrointestinal animal death, with 95% of the treated animals surviving for greater than 30 days.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Survival-
dc.subject.meshDose-Response Relationship, Radiation-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshGamma Rays-
dc.subject.meshIntestinal Diseases-
dc.subject.meshIntestine, Small-
dc.subject.meshMice-
dc.subject.meshMice, Inbred Strains-
dc.subject.meshRadiation Injuries, Experimental-
dc.subject.meshRadiation-Protective Agents-
dc.subject.meshStem Cells-
dc.subject.meshTransforming Growth Factor beta-
dc.titlePretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.en
dc.identifier.journalBritish Journal of Canceren
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