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dc.contributor.authorPotten, Christopher S
dc.contributor.authorBooth, Dawn
dc.contributor.authorHaley, J D
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.
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
html.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.


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