Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

2.50
Hdl Handle:
http://hdl.handle.net/10541/95960
Title:
Post-irradiation somatic mutation and clonal stabilisation time in the human colon.
Authors:
Campbell, F; Williams, G T; Appleton, M A; Dixon, M F; Harris, Martin; Williams, E D
Abstract:
BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.
Affiliation:
Department of Pathology, University of Wales, College of Medicine, Cardiff.
Citation:
Post-irradiation somatic mutation and clonal stabilisation time in the human colon. 1996, 39 (4):569-73 Gut
Journal:
Gut
Issue Date:
Oct-1996
URI:
http://hdl.handle.net/10541/95960
DOI:
10.1136/gut.39.4.569
PubMed ID:
8944567
Type:
Article
Language:
en
ISSN:
0017-5749
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorCampbell, Fen
dc.contributor.authorWilliams, G Ten
dc.contributor.authorAppleton, M Aen
dc.contributor.authorDixon, M Fen
dc.contributor.authorHarris, Martinen
dc.contributor.authorWilliams, E Den
dc.date.accessioned2010-04-08T10:28:49Z-
dc.date.available2010-04-08T10:28:49Z-
dc.date.issued1996-10-
dc.identifier.citationPost-irradiation somatic mutation and clonal stabilisation time in the human colon. 1996, 39 (4):569-73 Guten
dc.identifier.issn0017-5749-
dc.identifier.pmid8944567-
dc.identifier.doi10.1136/gut.39.4.569-
dc.identifier.urihttp://hdl.handle.net/10541/95960-
dc.description.abstractBACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.en
dc.language.isoenen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCell Division-
dc.subject.meshClone Cells-
dc.subject.meshColon-
dc.subject.meshEpithelium-
dc.subject.meshFemale-
dc.subject.meshHistocytochemistry-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMutation-
dc.subject.meshPhenotype-
dc.subject.meshStem Cells-
dc.subject.meshTime Factors-
dc.titlePost-irradiation somatic mutation and clonal stabilisation time in the human colon.en
dc.typeArticleen
dc.contributor.departmentDepartment of Pathology, University of Wales, College of Medicine, Cardiff.en
dc.identifier.journalGuten
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