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XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility
Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygo...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185405/ https://www.ncbi.nlm.nih.gov/pubmed/21737425 http://dx.doi.org/10.1093/nar/gkr280 |
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author | McNeill, Daniel R. Lin, Ping-Chang Miller, Marshall G. Pistell, Paul J. de Souza-Pinto, Nadja C. Fishbein, Kenneth W. Spencer, Richard G. Liu, Yie Pettan-Brewer, Christina Ladiges, Warren C. Wilson, David M. |
author_facet | McNeill, Daniel R. Lin, Ping-Chang Miller, Marshall G. Pistell, Paul J. de Souza-Pinto, Nadja C. Fishbein, Kenneth W. Spencer, Richard G. Liu, Yie Pettan-Brewer, Christina Ladiges, Warren C. Wilson, David M. |
author_sort | McNeill, Daniel R. |
collection | PubMed |
description | Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated—weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity—HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure. |
format | Online Article Text |
id | pubmed-3185405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-31854052011-10-04 XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility McNeill, Daniel R. Lin, Ping-Chang Miller, Marshall G. Pistell, Paul J. de Souza-Pinto, Nadja C. Fishbein, Kenneth W. Spencer, Richard G. Liu, Yie Pettan-Brewer, Christina Ladiges, Warren C. Wilson, David M. Nucleic Acids Res Genome Integrity, Repair and Replication Oxidative DNA damage plays a role in disease development and the aging process. A prominent participant in orchestrating the repair of oxidative DNA damage, particularly single-strand breaks, is the scaffold protein XRCC1. A series of chronological and biological aging parameters in XRCC1 heterozygous (HZ) mice were examined. HZ and wild-type (WT) C57BL/6 mice exhibit a similar median lifespan of ~26 months and a nearly identical maximal life expectancy of ~37 months. However, a number of HZ animals (7 of 92) showed a propensity for abdominal organ rupture, which may stem from developmental abnormalities given the prominent role of XRCC1 in endoderm and mesoderm formation. For other end-points evaluated—weight, fat composition, blood chemistries, condition of major organs, tissues and relevant cell types, behavior, brain volume and function, and chromosome and telomere integrity—HZ mice exhibited by-and-large a normal phenotype. Treatment of animals with the alkylating agent azoxymethane resulted in both liver toxicity and an increased incidence of precancerous lesions in the colon of HZ mice. Our study indicates that XRCC1 haploinsufficiency in mammals has little effect on chronological longevity and many key biological markers of aging in the absence of environmental challenges, but may adversely affect normal animal development or increase disease susceptibility to a relevant genotoxic exposure. Oxford University Press 2011-10 2011-07-06 /pmc/articles/PMC3185405/ /pubmed/21737425 http://dx.doi.org/10.1093/nar/gkr280 Text en Published by Oxford University Press 2011. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Genome Integrity, Repair and Replication McNeill, Daniel R. Lin, Ping-Chang Miller, Marshall G. Pistell, Paul J. de Souza-Pinto, Nadja C. Fishbein, Kenneth W. Spencer, Richard G. Liu, Yie Pettan-Brewer, Christina Ladiges, Warren C. Wilson, David M. XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title | XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title_full | XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title_fullStr | XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title_full_unstemmed | XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title_short | XRCC1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
title_sort | xrcc1 haploinsufficiency in mice has little effect on aging, but adversely modifies exposure-dependent susceptibility |
topic | Genome Integrity, Repair and Replication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3185405/ https://www.ncbi.nlm.nih.gov/pubmed/21737425 http://dx.doi.org/10.1093/nar/gkr280 |
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