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Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice

Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonst...

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Autores principales: Morita, Akinori, Wang, Bing, Tanaka, Kaoru, Katsube, Takanori, Murakami, Masahiro, Shimokawa, Takashi, Nishiyama, Yuichi, Ochi, Shintaro, Satoh, Hidetoshi, Nenoi, Mitsuru, Aoki, Shin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744379/
https://www.ncbi.nlm.nih.gov/pubmed/33344403
http://dx.doi.org/10.3389/fpubh.2020.601124
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author Morita, Akinori
Wang, Bing
Tanaka, Kaoru
Katsube, Takanori
Murakami, Masahiro
Shimokawa, Takashi
Nishiyama, Yuichi
Ochi, Shintaro
Satoh, Hidetoshi
Nenoi, Mitsuru
Aoki, Shin
author_facet Morita, Akinori
Wang, Bing
Tanaka, Kaoru
Katsube, Takanori
Murakami, Masahiro
Shimokawa, Takashi
Nishiyama, Yuichi
Ochi, Shintaro
Satoh, Hidetoshi
Nenoi, Mitsuru
Aoki, Shin
author_sort Morita, Akinori
collection PubMed
description Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation.
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spelling pubmed-77443792020-12-18 Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice Morita, Akinori Wang, Bing Tanaka, Kaoru Katsube, Takanori Murakami, Masahiro Shimokawa, Takashi Nishiyama, Yuichi Ochi, Shintaro Satoh, Hidetoshi Nenoi, Mitsuru Aoki, Shin Front Public Health Public Health Radiation damage to normal tissues is one of the most serious concerns in radiation therapy, and the tolerance dose of the normal tissues limits the therapeutic dose to the patients. p53 is well known as a transcription factor closely associated with radiation-induced cell death. We recently demonstrated the protective effects of several p53 regulatory agents against low-LET X- or γ-ray-induced damage. Although it was reported that high-LET heavy ion radiation (>85 keV/μm) could cause p53-independent cell death in some cancer cell lines, whether there is any radioprotective effect of the p53 regulatory agents against the high-LET radiation injury in vivo is still unclear. In the present study, we verified the efficacy of these agents on bone marrow and intestinal damages induced by high-LET heavy-ion irradiation in mice. We used a carbon-beam (14 keV/μm) that was shown to induce a p53-dependent effect and an iron-beam (189 keV/μm) that was shown to induce a p53-independent effect in a previous study. Vanadate significantly improved 60-day survival rate in mice treated with total-body carbon-ion (p < 0.0001) or iron-ion (p < 0.05) irradiation, indicating its effective protection of the hematopoietic system from radiation injury after high-LET irradiation over 85 keV/μm. 5CHQ also significantly increased the survival rate after abdominal carbon-ion (p < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7744379/ /pubmed/33344403 http://dx.doi.org/10.3389/fpubh.2020.601124 Text en Copyright © 2020 Morita, Wang, Tanaka, Katsube, Murakami, Shimokawa, Nishiyama, Ochi, Satoh, Nenoi and Aoki. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Public Health
Morita, Akinori
Wang, Bing
Tanaka, Kaoru
Katsube, Takanori
Murakami, Masahiro
Shimokawa, Takashi
Nishiyama, Yuichi
Ochi, Shintaro
Satoh, Hidetoshi
Nenoi, Mitsuru
Aoki, Shin
Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title_full Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title_fullStr Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title_full_unstemmed Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title_short Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice
title_sort protective effects of p53 regulatory agents against high-let radiation-induced injury in mice
topic Public Health
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744379/
https://www.ncbi.nlm.nih.gov/pubmed/33344403
http://dx.doi.org/10.3389/fpubh.2020.601124
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