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

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...

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Autores principales: Potten, C. S., Booth, D., Haley, J. D.
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223492/
https://www.ncbi.nlm.nih.gov/pubmed/9166937
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author Potten, C. S.
Booth, D.
Haley, J. D.
author_facet Potten, C. S.
Booth, D.
Haley, J. D.
author_sort Potten, C. S.
collection PubMed
description 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.
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spelling pubmed-22234922009-09-10 Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo. Potten, C. S. Booth, D. Haley, J. D. Br J Cancer Research Article 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. Nature Publishing Group 1997 /pmc/articles/PMC2223492/ /pubmed/9166937 Text en https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Potten, C. S.
Booth, D.
Haley, J. D.
Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title_full Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title_fullStr Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title_full_unstemmed Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title_short Pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
title_sort pretreatment with transforming growth factor beta-3 protects small intestinal stem cells against radiation damage in vivo.
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2223492/
https://www.ncbi.nlm.nih.gov/pubmed/9166937
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