The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine.

2.50
Hdl Handle:
http://hdl.handle.net/10541/85736
Title:
The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine.
Authors:
Potten, Christopher S; O'Shea, Julie A; Farrell, Catherine L; Rex, Karen; Booth, Catherine
Abstract:
Keratinocyte growth factor (KGF) administered on a daily basis for 3 or more days can result in dramatic changes in tissue architecture, particularly the thickness in oral epithelia, and can afford protection against the cytotoxic effects of radiation on the clonogenic stem cells in the crypts. This protection of intestinal stem cells (increased numbers of surviving crypts) is reflected in an increased survival of animals exposed to a lethal dose of irradiation. The mechanisms underlying these effects are not clear. The present experiments were designed to investigate the nature of any proliferative changes induced in the crypts of the small intestine by protracted exposure to KGF. Tritiated thymidine or bromodeoxyuridine labeling showed statistically significant increases in labeling in the stem cell zone of the crypt, with a concomitant reduction in labeling in the upper regions of the crypt corresponding to the late-dividing transit population. The increase in labeling in the lower regions of the crypt was also observed with Ki-67 staining, but the reduction in the upper regions of the crypt seen with tritiated thymidine was not observed with Ki-67. Metaphase arrest data suggest that the rate of progression through the cell cycle is essentially the same in KGF-treated animals as in controls, but there is a statistically significant increase in the number of mitotic events per crypt. Double labeling studies suggest that, at certain times of the day, there is a greater influx into S phase than efflux. The data overall indicate that KGF induces some complex proliferative changes in the intestinal crypts and are consistent with the hypothesis that the radioprotection may be afforded, at least in part, by a KGF-induced increase in stem cell numbers and/or increases in the number of stem cells in the S phase of the cell cycle. This alteration in the homeostasis of the crypt is compensated for by a foreshortening of the dividing transit lineage.
Affiliation:
Epithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom. cpotten@picr.man.ac.uk
Citation:
The effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine. 2001, 12 (5):265-75 Cell Growth Differ.
Journal:
Cell Growth & Differentiation
Issue Date:
May-2001
URI:
http://hdl.handle.net/10541/85736
PubMed ID:
11373273
Type:
Article
Language:
en
ISSN:
1044-9523
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorO'Shea, Julie Aen
dc.contributor.authorFarrell, Catherine Len
dc.contributor.authorRex, Karenen
dc.contributor.authorBooth, Catherineen
dc.date.accessioned2009-11-10T10:08:08Z-
dc.date.available2009-11-10T10:08:08Z-
dc.date.issued2001-05-
dc.identifier.citationThe effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine. 2001, 12 (5):265-75 Cell Growth Differ.en
dc.identifier.issn1044-9523-
dc.identifier.pmid11373273-
dc.identifier.urihttp://hdl.handle.net/10541/85736-
dc.description.abstractKeratinocyte growth factor (KGF) administered on a daily basis for 3 or more days can result in dramatic changes in tissue architecture, particularly the thickness in oral epithelia, and can afford protection against the cytotoxic effects of radiation on the clonogenic stem cells in the crypts. This protection of intestinal stem cells (increased numbers of surviving crypts) is reflected in an increased survival of animals exposed to a lethal dose of irradiation. The mechanisms underlying these effects are not clear. The present experiments were designed to investigate the nature of any proliferative changes induced in the crypts of the small intestine by protracted exposure to KGF. Tritiated thymidine or bromodeoxyuridine labeling showed statistically significant increases in labeling in the stem cell zone of the crypt, with a concomitant reduction in labeling in the upper regions of the crypt corresponding to the late-dividing transit population. The increase in labeling in the lower regions of the crypt was also observed with Ki-67 staining, but the reduction in the upper regions of the crypt seen with tritiated thymidine was not observed with Ki-67. Metaphase arrest data suggest that the rate of progression through the cell cycle is essentially the same in KGF-treated animals as in controls, but there is a statistically significant increase in the number of mitotic events per crypt. Double labeling studies suggest that, at certain times of the day, there is a greater influx into S phase than efflux. The data overall indicate that KGF induces some complex proliferative changes in the intestinal crypts and are consistent with the hypothesis that the radioprotection may be afforded, at least in part, by a KGF-induced increase in stem cell numbers and/or increases in the number of stem cells in the S phase of the cell cycle. This alteration in the homeostasis of the crypt is compensated for by a foreshortening of the dividing transit lineage.en
dc.language.isoenen
dc.subject.meshAnimals-
dc.subject.meshCell Division-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshDrug Administration Schedule-
dc.subject.meshFibroblast Growth Factor 7-
dc.subject.meshFibroblast Growth Factors-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshIntestine, Small-
dc.subject.meshKeratinocytes-
dc.subject.meshKi-67 Antigen-
dc.subject.meshMale-
dc.subject.meshMetaphase-
dc.subject.meshMice-
dc.subject.meshMice, Inbred BALB C-
dc.subject.meshMitosis-
dc.subject.meshRecombinant Proteins-
dc.subject.meshS Phase-
dc.titleThe effects of repeated doses of keratinocyte growth factor on cell proliferation in the cellular hierarchy of the crypts of the murine small intestine.en
dc.typeArticleen
dc.contributor.departmentEpithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, M20 4BX, United Kingdom. cpotten@picr.man.ac.uken
dc.identifier.journalCell Growth & Differentiationen

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