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Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations

Radiation-induced G(1) arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/–) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP5...

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Autores principales: Boyle, J M, Greaves, M J, Camplejohn, R S, Birch, J M, Roberts, S A, Varley, J M
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362814/
https://www.ncbi.nlm.nih.gov/pubmed/10206274
http://dx.doi.org/10.1038/sj.bjc.6690265
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author Boyle, J M
Greaves, M J
Camplejohn, R S
Birch, J M
Roberts, S A
Varley, J M
author_facet Boyle, J M
Greaves, M J
Camplejohn, R S
Birch, J M
Roberts, S A
Varley, J M
author_sort Boyle, J M
collection PubMed
description Radiation-induced G(1) arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/–) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon–intron boundaries, 3′ and 5′ untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G(1) arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/–) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G(1) arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent. © 1999 Cancer Research Campaign
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spelling pubmed-23628142009-09-10 Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations Boyle, J M Greaves, M J Camplejohn, R S Birch, J M Roberts, S A Varley, J M Br J Cancer Regular Article Radiation-induced G(1) arrest was studied in four classes of early passage skin fibroblasts comprising 12 normals, 12 heterozygous (mut/wt) TP53 mutation-carriers, two homozygous (mut/–) TP53 mutation-carriers and 16 strains from nine Li-Fraumeni syndrome or Li-Fraumeni-like families in which no TP53 mutation has been found, despite sequencing of all exons, exon–intron boundaries, 3′ and 5′ untranslated regions and promoter regions. In an assay of p53 allelic expression in yeast, cDNAs from these non-mutation strains behaved as wild-type p53. Using two different assays, we found G(1) arrest was reduced in heterozygous strains with mis-sense mutations and one truncation mutation, when compared to the range established for the normal cells. Heterozygous strains with mutations at splice sites behaved like normal cells, whilst homozygous (mut/–) strains showed either extremely reduced, or no, arrest. Strains from all nine non-mutation families gave responses within the normal range. Exceptions to the previously reported inverse correlation between G(1) arrest and clonogenic radiation resistance were observed, indicating that these phenotypes are not strictly interdependent. © 1999 Cancer Research Campaign Nature Publishing Group 1999-04 /pmc/articles/PMC2362814/ /pubmed/10206274 http://dx.doi.org/10.1038/sj.bjc.6690265 Text en Copyright © 1999 Cancer Research Campaign 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 Regular Article
Boyle, J M
Greaves, M J
Camplejohn, R S
Birch, J M
Roberts, S A
Varley, J M
Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title_full Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title_fullStr Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title_full_unstemmed Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title_short Radiation-induced G(1) arrest is not defective in fibroblasts from Li-Fraumeni families without TP53 mutations
title_sort radiation-induced g(1) arrest is not defective in fibroblasts from li-fraumeni families without tp53 mutations
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2362814/
https://www.ncbi.nlm.nih.gov/pubmed/10206274
http://dx.doi.org/10.1038/sj.bjc.6690265
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