scholarly journals Early Biomarkers Associated with P53 Signaling for Acute Radiation Injury

Life ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 99
Author(s):  
Weihong Li ◽  
Shixiang Zhou ◽  
Meng Jia ◽  
Xiaoxin Li ◽  
Lin Li ◽  
...  

Accurate dose assessment within 1 day or even 12 h after exposure through current methods of dose estimation remains a challenge, in response to a large number of casualties caused by nuclear or radiation accidents. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The expression levels of candidate genes were detected by RT-PCR. The expressions of screened DDB2, AEN, TRIAP1, and TRAF4 were stable in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2–24 h after irradiation. They are early indicators for medical treatment in acute radiation injury. Their effective combination could achieve a more accurate dose assessment for large-scale wounded patients within 24 h post exposure. The effective combination of p53-related genes DDB2, AEN, TRIAP1, and TRAF4 is a novel biodosimetry for a large number of people exposed to acute nuclear accidents.

2021 ◽  
Author(s):  
Weihong Li ◽  
Shixiang Zhou ◽  
Meng Jia ◽  
Xiaoxin Li ◽  
Lin Li ◽  
...  

Abstract Background: Rapid and accurate high-throughput estimation of radiation dose aims to help medical rescue in nuclear radiation accident. However, current methods of dose estimation are still lacking of speedy or accuracy. P53 signaling pathway plays an important role in DNA damage repair and cell apoptosis induced by ionizing radiation. The changes of radiation-induced P53 related genes in the early stage of ionizing radiation should compensate for the deficiency of lymphocyte decline and γ-H2AX analysis as novel biomarkers of radiation damage. Methods: Bioinformatic analysis was performed on previous data to find candidate genes from human peripheral blood irradiated in vitro. The radiation sensitivity and baseline levels of candidate genes were verified. The approximate threshold for guiding medical treatment was estimated for each gene, and four genes were combined to construct an effectively early dose estimation model of radiation.Results: Four p53-related genes, DDB2, AEN, TRIAP1 and TRAF4, were screened and verified their significant radiosensitivity. Their expressions were stable without gender or age difference in healthy population, but significantly up-regulated by radiation, with time specificity and dose dependence in 2h-24h after irradiation. Further studies showed these genes can be used as indicators for early medical treatment in acute radiation injury. The effective combination of the four genes could achieve a more accurate dose assessment and injury classification for large-scale wounded patients within 24 hours post exposure.Conclusions: This is the first time to investigate the potential biomarkers of ionizing radiation by systematic study. The effective combination of the four genes provides a new model for dose estimation and injury classification of a large number of exposed population in acute nuclear accidents, and also provides a new idea and method.


2018 ◽  
Vol 13 (02) ◽  
pp. 197-202
Author(s):  
Sandeep Kumar Soni ◽  
Mitra Basu ◽  
Priyanka Agrawal ◽  
Aseem Bhatnagar ◽  
Neelam Chhillar

AbstractObjectiveResearchers have been evaluating several approaches to assess acute radiation injury/toxicity markers owing to radiation exposure. Keeping in mind this background, we assumed that whole-body irradiation in single fraction in graded doses can affect the antioxidant profile in skin that could be used as an acute radiation injury/toxicity marker.MethodsSprague-Dawley rats were treated with CO-60 gamma radiation (dose: 1-5 Gy; dose rate: 0.85 Gy/minute). Skin samples were collected (before and after radiation up to 72 hours) and analyzed for glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPx).ResultsIntra-group comparison showed significant differences in GSH, GPx, SOD, and CAT, and they declined in a dose-dependent manner from 1 to 5 Gy (P value<0.01, r value: 0.3-0.5). LPx value increased (P value<0.01, r value: 0.3-0.5) as the dose increased, except in 1 Gy (P value>0.05).ConclusionsThis study suggests that skin antioxidants were sensitive toward radiation even at a low radiation dose, which can be used as a predictor of radiation injury and altered in a dose-dependent manner. These biochemical parameters may have wider application in the evaluation of radiation-induced skin injury and dose assessment. (Disaster Med Public Health Preparedness. 2019;13:197–202).


PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e30434 ◽  
Author(s):  
Lena A. Basile ◽  
Dolph Ellefson ◽  
Zoya Gluzman-Poltorak ◽  
Katiana Junes-Gill ◽  
Vernon Mar ◽  
...  

2021 ◽  
Author(s):  
W. June Brickey ◽  
Michael A. Thompson ◽  
Zhecheng Sheng ◽  
Zhiguo Li ◽  
Kouros Owzar ◽  
...  

Radiation can be applied for therapeutic benefit against cancer or may result in devastating harm due to accidental or intentional release of nuclear energy. In all cases, radiation exposure causes molecular and cellular damage, resulting in the production of inflammatory factors and danger signals. Several classes of innate immune receptors sense the released damage associated molecules and activate cellular response pathways, including the induction of inflammasome signaling that impacts IL-1β/IL-18 maturation and cell death. A previous report indicated inflammasomes aggravate acute radiation syndrome. In contrast, here we find that inflammasome components do not exacerbate gamma-radiation-induced injury by examining heterozygous and gene-deletion littermate controls in addition to wild-type mice. Absence of some inflammasome genes, such as caspase-1/11 and Nlrp3, enhance susceptibility of treated mice to acute radiation injury, indicating importance of the inflammasome pathway in radioprotection. Surprisingly, we discover that the survival outcome may be sex-dependent as more inflammasome-deficient male mice are susceptible to radiation-induced injury. We discuss parameters that may influence the role of inflammasomes as radioprotective or radioexacerbating factors in recovery from radiation injury including the use of littermate controls, the sex of the animals, differences in microbiota within the colonies and other experimental conditions. Under the conditions tested, inflammasome components do not exacerbate radiation injury, but rather provide protective benefit.


2020 ◽  
Vol 78 ◽  
pp. 103395
Author(s):  
Mutsumi Matsuu-Matsuyama ◽  
Kazuko Shichijo ◽  
Takashi Tsuchiya ◽  
Hisayoshi Kondo ◽  
Shiro Miura ◽  
...  

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