Breath biomarkers of total body irradiation in non-human primates

2021 ◽  
Author(s):  
Michael Phillips ◽  
Felix Grun ◽  
Peter Schmitt
Keyword(s):  
Oxidative Stress ◽  
Radiation Exposure ◽  
Cumulative Dose ◽  
Total Body Irradiation ◽  
Background Radiation ◽  
Gas Chromatography Mass Spectrometry ◽  
Metabolic Products ◽  
Volatile Organic ◽  
Total Body ◽  
Radiation Biodosimetry

Abstract Background: Radiation exposure causes oxidative stress, eliciting production of metabolites that are exhaled in the breath as volatile organic compounds (VOCs). We evaluated breath VOCs as potential biomarkers for use in radiation biodosimetry. Methods: Five anesthetized non-human primates receive total body irradiation (TBI) of three daily fractions of 120 cGy per day for three days, resulting in a cumulative dose of 10.8 Gy. Breath samples were collected prior to irradiation and after each radiation fraction, and analyzed with gas chromatography mass spectrometry. Results: TBI elicited a prompt and statistically significant increase in the abundance of several hundred VOCs in the breath, including some that were increased more than five-fold, with100% sensitivity and 100% specificity for radiation exposure. The most significant breath VOC biomarkers of radiation mainly comprised straight-chain n-alkanes (e.g. hexane), as well as methylated alkanes (e.g. 3-methyl-pentane) and alkane derivatives (e.g. 2-butyl-1-octanol), consistent with metabolic products of oxidative stress. An unidentified breath VOC biomarker increased more than ten-fold following TBI, and rose linearly with the total cumulative dose of radiation (R2=0.92). Conclusions: TBI of non-human primates elicited increased production of breath VOCs consistent with increased oxidative stress. These findings provide a rational basis for further evaluation of breath VOC biomarkers in human radiation biodosimetry.

Radiation-induced kidney injury

2019 ◽  
Vol 3 (3) ◽  
pp. 160-167 ◽  
Author(s):  
Jaya Kala
Keyword(s):  
Experimental Data ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Radiation Exposure ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Total Body Irradiation ◽  
Hematopoietic Stem ◽  
Total Body

Renal dysfunction because of radiation exposure was recognized decades ago. The incidence declined when more effective chemotherapeutic agents became available. However, there appears to be a resurgence with the advent of total body irradiation used prior to hematopoietic stem cell transplantation. Several chemotherapeutic drugs used prior to total body irradiation have some ionizing radiation potentiating effects. Chronic kidney disease that occurs after hematopoietic stem cell transplantation is known to occur due to nephrotoxicity from medications, graft-versus-host disease, and the currently under-recognized radiation exposure. The clinical features vary depending on the dose of radiation and the volume of single or bilateral kidneys exposed. The usual symptoms of fatigue, edema, anemia, malignant hypertension, azotemia, and shortness of breath appear in 6–12 months of exposure. Since this is an under-recognized entity, there are no large controlled trials to guide therapy. This review highlights some of the experimental data that have shown some promising results for treatment. There is need for further studies on the current incidence and prevalence and clinical trials to guide treatment, based on the experimental data available.

Early-response Biomarkers for Assessment of Radiation Exposure in a Mouse Total-body Irradiation Model

2014 ◽  
Vol 106 (6) ◽  
pp. 772-786 ◽  
Author(s):  
Natalia I. Ossetrova ◽  
Donald P. Condliffe ◽  
Patrick H. Ney ◽  
Katya Krasnopolsky ◽  
Kevin P. Hieber ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Total Body Irradiation ◽  
Early Response ◽  
Total Body ◽  
Response Biomarkers

Total Body Irradiation Causes Residual Bone Marrow Injury by Induction of Persistent Oxidative Stress in Murine Hematopoietic Stem Cells.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3209-3209
Author(s):  
Yong Wang ◽  
Lingbo Liu ◽  
Senthil Kumar Pazhanisamy ◽  
Aimin Meng ◽  
Daohong Zhou
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Total Body Irradiation ◽  
Molecular Mechanisms ◽  
Conflicts Of Interest ◽  
Tissue Injury ◽  
Hematopoietic Stem ◽  
Chronic Oxidative Stress ◽  
Total Body

Abstract Abstract 3209 Poster Board III-146 Ionizing radiation (IR) and/or chemotherapy cause not only acute tissue injury but also have late effects including long-term bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to induction of hematopoietic stem cell (HSC) senescence. However, neither the molecular mechanisms by which IR and/or chemotherapy induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury, which were investigated in the present study using a total body irradiation (TBI) mouse model. The results showed that exposure of mice to 6.5 Gy TBI induced a persistent increase in reactive oxygen species (ROS) production in HSCs only for up to 8 weeks, primarily via up-regulation of NADPH oxidase 4 (NOX4). This finding provides the foremost direct evidence demonstrating that in vivo exposure to IR causes persistent oxidative stress selectively in a specific population of BM hematopoietic cells (HSCs). The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double strand breaks, inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetyl-cysteine (NAC) after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. These findings suggest that selective induction of chronic oxidative stress in HSCs by TBI leads to induction of HSC senescence and residual BM injury and that antioxidant therapy may be used as an effective strategy to mitigate IR- and chemotherapy-induced residual BM injury. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical summary guide: reproduction in women with previous abdominopelvic radiotherapy or total body irradiation

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
G Rozen ◽  
P Rogers ◽  
S Chander ◽  
R Anderson ◽  
O McNally ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Total Body Irradiation ◽  
English Language ◽  
Conflicts Of Interest ◽  
Case Reports ◽  
Adult Women ◽  
Patient Counselling ◽  
Uncomplicated Pregnancy ◽  
Total Body ◽  
The Impact

Abstract STUDY QUESTION What is the evidence to guide the management of women who wish to conceive following abdominopelvic radiotherapy (AP RT) or total body irradiation (TBI)? SUMMARY ANSWER Pregnancy is possible, even following higher doses of post-pubertal uterine radiation exposure; however, it is associated with adverse reproductive sequelae and pregnancies must be managed in a high-risk obstetric unit. WHAT IS KNOWN ALREADY In addition to primary ovarian insufficiency, female survivors who are treated with AP RT and TBI are at risk of damage to the uterus. This may impact on its function and manifest as adverse reproductive sequelae. STUDY DESIGN, SIZE, DURATION A review of the literature was carried out and a multidisciplinary working group provided expert opinion regarding assessment of the uterus and obstetric management. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive outcomes for postpubertal women with uterine radiation exposure in the form of AP RT or TBI were reviewed. This included Pubmed listed peer-reviewed publications from 1990 to 2019, and limited to English language.. MAIN RESULTS AND THE ROLE OF CHANCE The prepubertal uterus is much more vulnerable to the effects of radiation than after puberty. Almost all available information about the impact of radiation on the uterus comes from studies of radiation exposure during childhood or adolescence. An uncomplicated pregnancy is possible, even with doses as high as 54 Gy. Therefore, tumour treatment doses alone cannot at present be used to accurately predict uterine damage. LIMITATIONS, REASONS FOR CAUTION Much of the data cannot be readily extrapolated to adult women who have had uterine radiation and the publications concerning adult women treated with AP RT are largely limited to case reports. WIDER IMPLICATIONS OF THE FINDINGS This analysis offers clinical guidance and assists with patient counselling. It is important to include patients who have undergone AP RT or TBI in prospective studies to provide further evidence regarding uterine function, pregnancy outcomes and correlation of imaging with clinical outcomes. STUDY FUNDING/COMPETING INTEREST(S) This study received no funding and there are no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

scholarly journals Sublethal Total Body Irradiation Leads to Early Cerebellar Damage and Oxidative Stress

2010 ◽  
Vol 7 (2) ◽  
pp. 125-135 ◽  
Author(s):  
Li Cui ◽  
Dwight Pierce ◽  
Kim E. Light ◽  
Russell B. Melchert ◽  
Qiang Fu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Total Body Irradiation ◽  
Cerebellar Damage ◽  
Total Body ◽  
And Oxidative Stress
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