Human colonic stem cell mutation frequency with and without irradiation
Mild periodic acid‐Schiff (mPAS) staining distinguishes O‐acetylated from non‐O‐acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS‐positive (non‐O‐acetylated), uniformly mPAS‐negative (O‐acetylated), and negative with infrequent scatte...
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| Veröffentlicht in: | The Journal of pathology 1994-11, Vol.174 (3), p.175-182 |
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| creator | Campbell, Fiona Fuller, Clare E. Williams, Geraint T. Williams, E. Dillwyn |
| description | Mild periodic acid‐Schiff (mPAS) staining distinguishes O‐acetylated from non‐O‐acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS‐positive (non‐O‐acetylated), uniformly mPAS‐negative (O‐acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation‐induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but informative irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non‐irradiated 14·5 ± 8·2 × 10−4 vs. 6·1 ± 4·2 × 10−4). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7·5 ± 4·5 × 10−4 vs. 0·3 ± 0·5 × 10−4, Mann‐Whitney U, P |
| doi_str_mv | 10.1002/path.1711740306 |
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Dillwyn</creator><creatorcontrib>Campbell, Fiona ; Fuller, Clare E. ; Williams, Geraint T. ; Williams, E. Dillwyn</creatorcontrib><description>Mild periodic acid‐Schiff (mPAS) staining distinguishes O‐acetylated from non‐O‐acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS‐positive (non‐O‐acetylated), uniformly mPAS‐negative (O‐acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation‐induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but informative irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non‐irradiated 14·5 ± 8·2 × 10−4 vs. 6·1 ± 4·2 × 10−4). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7·5 ± 4·5 × 10−4 vs. 0·3 ± 0·5 × 10−4, Mann‐Whitney U, P<0·005). Two patients receiving radiotherapy many years before colectomy showed a very high total discordant crypt frequency but relatively few partially affected crypts. Studies of somatic mutation in colonic or small intestinal crypts following a single dose of mutagen in mice have shown early partial crypt involvement by the mutated phenotype and later complete crypt involvement. The demonstration in man that recent radiation greatly increases the frequency of partially involved discordant crypts while long‐term radiation greatly increases the frequency of wholly involved discordant crypts confirms that the discordant crypts result from stem cell mutation in individuals heterozygous for a polymorphic gene controlling O‐acetylation of sialoglycoproteins. They show that the mPAS technique can be used to identify and quantify colonic stem cell somatic mutation in man.</description><identifier>ISSN: 0022-3417</identifier><identifier>EISSN: 1096-9896</identifier><identifier>DOI: 10.1002/path.1711740306</identifier><identifier>PMID: 7823250</identifier><identifier>CODEN: JPTLAS</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Aged ; Biological and medical sciences ; Colon ; Colon - chemistry ; Colon - radiation effects ; Female ; Humans ; Intestinal Mucosa - radiation effects ; Male ; Medical sciences ; Middle Aged ; Miscellaneous ; Mutation ; O-acetylation ; Periodic Acid-Schiff Reaction ; Phenotype ; radiation ; Rectal Neoplasms - genetics ; Rectal Neoplasms - pathology ; sialic acid ; Sialoglycoproteins - analysis ; Sialoglycoproteins - genetics ; somatic mutation ; Time Factors ; Traumas. Diseases due to physical agents</subject><ispartof>The Journal of pathology, 1994-11, Vol.174 (3), p.175-182</ispartof><rights>Copyright © 1994 John Wiley & Sons, Ltd.</rights><rights>1995 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4116-4c615d5bc8c5e1ebebb4165c5daab1b975f17ad6e2f5044b5084d8cce4dc2ad3</citedby><cites>FETCH-LOGICAL-c4116-4c615d5bc8c5e1ebebb4165c5daab1b975f17ad6e2f5044b5084d8cce4dc2ad3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpath.1711740306$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpath.1711740306$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3365414$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7823250$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Campbell, Fiona</creatorcontrib><creatorcontrib>Fuller, Clare E.</creatorcontrib><creatorcontrib>Williams, Geraint T.</creatorcontrib><creatorcontrib>Williams, E. Dillwyn</creatorcontrib><title>Human colonic stem cell mutation frequency with and without irradiation</title><title>The Journal of pathology</title><addtitle>J. Pathol</addtitle><description>Mild periodic acid‐Schiff (mPAS) staining distinguishes O‐acetylated from non‐O‐acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS‐positive (non‐O‐acetylated), uniformly mPAS‐negative (O‐acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation‐induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but informative irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non‐irradiated 14·5 ± 8·2 × 10−4 vs. 6·1 ± 4·2 × 10−4). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7·5 ± 4·5 × 10−4 vs. 0·3 ± 0·5 × 10−4, Mann‐Whitney U, P<0·005). Two patients receiving radiotherapy many years before colectomy showed a very high total discordant crypt frequency but relatively few partially affected crypts. Studies of somatic mutation in colonic or small intestinal crypts following a single dose of mutagen in mice have shown early partial crypt involvement by the mutated phenotype and later complete crypt involvement. The demonstration in man that recent radiation greatly increases the frequency of partially involved discordant crypts while long‐term radiation greatly increases the frequency of wholly involved discordant crypts confirms that the discordant crypts result from stem cell mutation in individuals heterozygous for a polymorphic gene controlling O‐acetylation of sialoglycoproteins. They show that the mPAS technique can be used to identify and quantify colonic stem cell somatic mutation in man.</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Colon</subject><subject>Colon - chemistry</subject><subject>Colon - radiation effects</subject><subject>Female</subject><subject>Humans</subject><subject>Intestinal Mucosa - radiation effects</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Miscellaneous</subject><subject>Mutation</subject><subject>O-acetylation</subject><subject>Periodic Acid-Schiff Reaction</subject><subject>Phenotype</subject><subject>radiation</subject><subject>Rectal Neoplasms - genetics</subject><subject>Rectal Neoplasms - pathology</subject><subject>sialic acid</subject><subject>Sialoglycoproteins - analysis</subject><subject>Sialoglycoproteins - genetics</subject><subject>somatic mutation</subject><subject>Time Factors</subject><subject>Traumas. Diseases due to physical agents</subject><issn>0022-3417</issn><issn>1096-9896</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtLw0AQhxdRaq2ePQk5eE27m30kwVMN2gql9lAQvCz7Cl3No-4m1P73pg8qnjzNwHy_meED4BbBIYIwGq1FsxqiGKGYQAzZGegjmLIwTVJ2DvodEYWYoPgSXHn_ASFMU0p7oBcnEY4o7IPJtC1FFai6qCurAt-YMlCmKIKybURj6yrInflqTaW2wcY2q0BUet_UbRNY54S2e-waXOSi8ObmWAdg-fy0zKbh7HXyko1noSIIsZAohqimUiWKGmSkkZIgRhXVQkgk05jmKBaamSinkBBJYUJ0opQhWkVC4wEYHdYqV3vvTM7XzpbCbTmCfCeE74TwXyFd4u6QWLeyNPrEHw108_vjXHglityJSll_wjBmlCDSYQ8HbGMLs_3vKl-Ml9M_T4SHtO0Ef5_Swn1yFuOY8rf5hL9n6SKZP2Y8wT8mj4sZ</recordid><startdate>199411</startdate><enddate>199411</enddate><creator>Campbell, Fiona</creator><creator>Fuller, Clare E.</creator><creator>Williams, Geraint T.</creator><creator>Williams, E. Dillwyn</creator><general>John Wiley & Sons, Ltd</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>199411</creationdate><title>Human colonic stem cell mutation frequency with and without irradiation</title><author>Campbell, Fiona ; Fuller, Clare E. ; Williams, Geraint T. ; Williams, E. Dillwyn</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4116-4c615d5bc8c5e1ebebb4165c5daab1b975f17ad6e2f5044b5084d8cce4dc2ad3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Colon</topic><topic>Colon - chemistry</topic><topic>Colon - radiation effects</topic><topic>Female</topic><topic>Humans</topic><topic>Intestinal Mucosa - radiation effects</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Miscellaneous</topic><topic>Mutation</topic><topic>O-acetylation</topic><topic>Periodic Acid-Schiff Reaction</topic><topic>Phenotype</topic><topic>radiation</topic><topic>Rectal Neoplasms - genetics</topic><topic>Rectal Neoplasms - pathology</topic><topic>sialic acid</topic><topic>Sialoglycoproteins - analysis</topic><topic>Sialoglycoproteins - genetics</topic><topic>somatic mutation</topic><topic>Time Factors</topic><topic>Traumas. Diseases due to physical agents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Campbell, Fiona</creatorcontrib><creatorcontrib>Fuller, Clare E.</creatorcontrib><creatorcontrib>Williams, Geraint T.</creatorcontrib><creatorcontrib>Williams, E. Dillwyn</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Campbell, Fiona</au><au>Fuller, Clare E.</au><au>Williams, Geraint T.</au><au>Williams, E. Dillwyn</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human colonic stem cell mutation frequency with and without irradiation</atitle><jtitle>The Journal of pathology</jtitle><addtitle>J. Pathol</addtitle><date>1994-11</date><risdate>1994</risdate><volume>174</volume><issue>3</issue><spage>175</spage><epage>182</epage><pages>175-182</pages><issn>0022-3417</issn><eissn>1096-9896</eissn><coden>JPTLAS</coden><abstract>Mild periodic acid‐Schiff (mPAS) staining distinguishes O‐acetylated from non‐O‐acetylated sialoglycoproteins. In human colonic mucosa, individuals possess one of three phenotypes: uniformly mPAS‐positive (non‐O‐acetylated), uniformly mPAS‐negative (O‐acetylated), and negative with infrequent scattered positive crypts. This is due to a polymorphism in a single autosomal gene (oat). Discordant crypts have not been found in children's colons, suggesting that they result from somatic mutation in heterozygous individuals. We now present evidence to confirm this based on a study of radiation‐induced changes. Comparison of mPAS staining of large intestinal mucosa from patients given radiation 4 weeks before surgery for carcinoma of the rectum with matched controls receiving surgery alone showed a similar phenotype distribution, but informative irradiated patients showed an increased frequency of discordant crypts (irradiated vs. non‐irradiated 14·5 ± 8·2 × 10−4 vs. 6·1 ± 4·2 × 10−4). When these were classified as wholly or partially involved by the aberrant phenotype, the increase was most marked in partially involved crypts (7·5 ± 4·5 × 10−4 vs. 0·3 ± 0·5 × 10−4, Mann‐Whitney U, P<0·005). Two patients receiving radiotherapy many years before colectomy showed a very high total discordant crypt frequency but relatively few partially affected crypts. Studies of somatic mutation in colonic or small intestinal crypts following a single dose of mutagen in mice have shown early partial crypt involvement by the mutated phenotype and later complete crypt involvement. The demonstration in man that recent radiation greatly increases the frequency of partially involved discordant crypts while long‐term radiation greatly increases the frequency of wholly involved discordant crypts confirms that the discordant crypts result from stem cell mutation in individuals heterozygous for a polymorphic gene controlling O‐acetylation of sialoglycoproteins. They show that the mPAS technique can be used to identify and quantify colonic stem cell somatic mutation in man.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>7823250</pmid><doi>10.1002/path.1711740306</doi><tpages>8</tpages></addata></record> |
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| subjects | Aged Biological and medical sciences Colon Colon - chemistry Colon - radiation effects Female Humans Intestinal Mucosa - radiation effects Male Medical sciences Middle Aged Miscellaneous Mutation O-acetylation Periodic Acid-Schiff Reaction Phenotype radiation Rectal Neoplasms - genetics Rectal Neoplasms - pathology sialic acid Sialoglycoproteins - analysis Sialoglycoproteins - genetics somatic mutation Time Factors Traumas. Diseases due to physical agents |
| title | Human colonic stem cell mutation frequency with and without irradiation |
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