Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.

Exposure to ultraviolet (UV) light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavel...

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Autores principales:	Gillian D McFeat, Sarah L Allinson, Trevor J McMillan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/698c8fd5c8274177aa12a5d680915346
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spelling	oai:doaj.org-article:698c8fd5c8274177aa12a5d6809153462021-11-18T08:53:13ZCharacterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.1932-620310.1371/journal.pone.0075800https://doaj.org/article/698c8fd5c8274177aa12a5d6809153462013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24098727/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Exposure to ultraviolet (UV) light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavelengths of UV therefore remains an important aim so that risks and their moderation can be evaluated, in particular in relation to the initiation of skin cancer. The p53 tumour suppressor protein is central to the cellular response that protects the genome from damage by external agents such as UV, thus reducing the risk of tumorigenesis. In response to a variety of DNA damaging agents including UV light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating apoptosis and stimulating repair processes, all of which prevent the propagation of potentially mutagenic defects. In this study we examined the induction of p53 protein and its influence on the survival of primary mouse fibroblasts exposed to different wavelengths of UV light. UVC was found to elevate p53 protein and its sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to induce p53 protein accumulation or sequence specific DNA binding. Despite this, UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult. Thus, it is demonstrated that the elements of the p53 cellular response evoked by exposure to UV radiation are wavelength dependent. Furthermore, the interrelationship between various endpoints is complex and not easily predictable. This has important implications not only for understanding the mode of action of p53 but also for the use of molecular endpoints in quantifying exposure to different wavelengths of UV in the context of human health protection.Gillian D McFeatSarah L AllinsonTrevor J McMillanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e75800 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gillian D McFeat Sarah L Allinson Trevor J McMillan Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
description	Exposure to ultraviolet (UV) light can cause significant damage to mammalian cells and, although the spectrum of damage produced varies with the wavelength of UV, all parts of the UV spectrum are recognised as being detrimental to human health. Characterising the cellular response to different wavelengths of UV therefore remains an important aim so that risks and their moderation can be evaluated, in particular in relation to the initiation of skin cancer. The p53 tumour suppressor protein is central to the cellular response that protects the genome from damage by external agents such as UV, thus reducing the risk of tumorigenesis. In response to a variety of DNA damaging agents including UV light, wild-type p53 plays a role in mediating cell-cycle arrest, facilitating apoptosis and stimulating repair processes, all of which prevent the propagation of potentially mutagenic defects. In this study we examined the induction of p53 protein and its influence on the survival of primary mouse fibroblasts exposed to different wavelengths of UV light. UVC was found to elevate p53 protein and its sequence specific DNA binding capacity. Unexpectedly, UVA treatment failed to induce p53 protein accumulation or sequence specific DNA binding. Despite this, UVA exposure of wild-type cells induced a p53 dependent G1 cell cycle arrest followed by a wave of p53 dependent apoptosis, peaking 12 hours post-insult. Thus, it is demonstrated that the elements of the p53 cellular response evoked by exposure to UV radiation are wavelength dependent. Furthermore, the interrelationship between various endpoints is complex and not easily predictable. This has important implications not only for understanding the mode of action of p53 but also for the use of molecular endpoints in quantifying exposure to different wavelengths of UV in the context of human health protection.
format	article
author	Gillian D McFeat Sarah L Allinson Trevor J McMillan
author_facet	Gillian D McFeat Sarah L Allinson Trevor J McMillan
author_sort	Gillian D McFeat
title	Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
title_short	Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
title_full	Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
title_fullStr	Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
title_full_unstemmed	Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
title_sort	characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/698c8fd5c8274177aa12a5d680915346
work_keys_str_mv	AT gilliandmcfeat characterisationofthep53mediatedcellularresponsesevokedinprimarymousecellsfollowingexposuretoultravioletradiation AT sarahlallinson characterisationofthep53mediatedcellularresponsesevokedinprimarymousecellsfollowingexposuretoultravioletradiation AT trevorjmcmillan characterisationofthep53mediatedcellularresponsesevokedinprimarymousecellsfollowingexposuretoultravioletradiation
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Characterisation of the p53-mediated cellular responses evoked in primary mouse cells following exposure to ultraviolet radiation.

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