Post-irradiation somatic mutation and clonal stabilisation time in the human colon.
AffiliationDepartment of Pathology, University of Wales, College of Medicine, Cardiff.
MetadataShow full item record
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.
CitationPost-irradiation somatic mutation and clonal stabilisation time in the human colon. 1996, 39 (4):569-73 Gut
- Human colonic stem cell mutation frequency with and without irradiation.
- Authors: Campbell F, Fuller CE, Williams GT, Williams ED
- Issue date: 1994 Nov
- Crypt fission in the small intestine and colon. A mechanism for the emergence of G6PD locus-mutated crypts after treatment with mutagens.
- Authors: Park HS, Goodlad RA, Wright NA
- Issue date: 1995 Nov
- Mitochondrial DNA mutations are established in human colonic stem cells, and mutated clones expand by crypt fission.
- Authors: Greaves LC, Preston SL, Tadrous PJ, Taylor RW, Barron MJ, Oukrif D, Leedham SJ, Deheragoda M, Sasieni P, Novelli MR, Jankowski JA, Turnbull DM, Wright NA, McDonald SA
- Issue date: 2006 Jan 17
- A stem cell niche theory of intestinal crypt maintenance based on a study of somatic mutation in colonic mucosa.
- Authors: Williams ED, Lowes AP, Williams D, Williams GT
- Issue date: 1992 Oct
- Crypt-restricted metallothionein immunopositivity in murine colon: validation of a model for studies of somatic stem cell mutation.
- Authors: Anne Cook H, Williams D, Anne Thomas G
- Issue date: 2000 Jul