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The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates

BACKGROUND: The aim of the study was to clarify the effect of p53 status of tumor cells on radio-sensitivity of solid tumors following γ-ray irradiation at various dose rates, referring to the response of intratumor quiescent (Q) cells. METHODS: Human head and neck squamous cell carcinoma cells tran...

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Autores principales: Masunaga, Shin-ichiro, Kobayashi, Junya, Tano, Keizo, Sanada, Yu, Suzuki, Minoru, Ono, Koji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elmer Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188028/
https://www.ncbi.nlm.nih.gov/pubmed/30344816
http://dx.doi.org/10.14740/jocmr3610w
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author Masunaga, Shin-ichiro
Kobayashi, Junya
Tano, Keizo
Sanada, Yu
Suzuki, Minoru
Ono, Koji
author_facet Masunaga, Shin-ichiro
Kobayashi, Junya
Tano, Keizo
Sanada, Yu
Suzuki, Minoru
Ono, Koji
author_sort Masunaga, Shin-ichiro
collection PubMed
description BACKGROUND: The aim of the study was to clarify the effect of p53 status of tumor cells on radio-sensitivity of solid tumors following γ-ray irradiation at various dose rates, referring to the response of intratumor quiescent (Q) cells. METHODS: Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor bearing mice received 5-bromo-2’-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays at a high, middle or low dose rate. Immediately or 9 h after the high dose-rate irradiation (HDR, 2.5 Gy/min), or immediately after the middle (MDR, 0.039 Gy/min) or low (LDR, 0.00098 Gy/min) dose-rate irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. RESULTS: Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. The recovery capacities following γ-ray irradiation were greater in Q than total cell population and increased in the following order of 9 h after HDR < MDR < LDR. Thus, the difference in radio-sensitivity between the total (P + Q) and Q cells after γ-ray irradiation increased in the same order. CONCLUSION: To secure controlling solid tumors as a whole, difference in sensitivity between total and Q tumor cells especially in solid tumors irrespective of p53 status has to be suppressed as irradiation dose rate decreases, for instance, through employing combined method for enhancing the response of Q tumor cells.
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spelling pubmed-61880282018-10-19 The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates Masunaga, Shin-ichiro Kobayashi, Junya Tano, Keizo Sanada, Yu Suzuki, Minoru Ono, Koji J Clin Med Res Original Article BACKGROUND: The aim of the study was to clarify the effect of p53 status of tumor cells on radio-sensitivity of solid tumors following γ-ray irradiation at various dose rates, referring to the response of intratumor quiescent (Q) cells. METHODS: Human head and neck squamous cell carcinoma cells transfected with mutant TP53 (SAS/mp53) or with neo vector (SAS/neo) were injected subcutaneously into hind legs of nude mice. Tumor bearing mice received 5-bromo-2’-deoxyuridine (BrdU) continuously to label all intratumor proliferating (P) cells. They received γ-rays at a high, middle or low dose rate. Immediately or 9 h after the high dose-rate irradiation (HDR, 2.5 Gy/min), or immediately after the middle (MDR, 0.039 Gy/min) or low (LDR, 0.00098 Gy/min) dose-rate irradiation, the tumor cells were isolated and incubated with a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. RESULTS: Following γ-ray irradiation, SAS/neo tumor cells, especially intratumor Q cells, showed a marked reduction in sensitivity due to the recovery from radiation-induced damage, compared with the total or Q cells within SAS/mp53 tumors that showed little repair capacity. The recovery capacities following γ-ray irradiation were greater in Q than total cell population and increased in the following order of 9 h after HDR < MDR < LDR. Thus, the difference in radio-sensitivity between the total (P + Q) and Q cells after γ-ray irradiation increased in the same order. CONCLUSION: To secure controlling solid tumors as a whole, difference in sensitivity between total and Q tumor cells especially in solid tumors irrespective of p53 status has to be suppressed as irradiation dose rate decreases, for instance, through employing combined method for enhancing the response of Q tumor cells. Elmer Press 2018-11 2018-10-09 /pmc/articles/PMC6188028/ /pubmed/30344816 http://dx.doi.org/10.14740/jocmr3610w Text en Copyright 2018, Masunaga et al. http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Masunaga, Shin-ichiro
Kobayashi, Junya
Tano, Keizo
Sanada, Yu
Suzuki, Minoru
Ono, Koji
The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title_full The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title_fullStr The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title_full_unstemmed The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title_short The Effect of p53 Status on Radio-Sensitivity of Quiescent Tumor Cell Population Irradiated With γ-Rays at Various Dose Rates
title_sort effect of p53 status on radio-sensitivity of quiescent tumor cell population irradiated with γ-rays at various dose rates
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6188028/
https://www.ncbi.nlm.nih.gov/pubmed/30344816
http://dx.doi.org/10.14740/jocmr3610w
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