All for one, though not one for all: team players in normal tissue radiobiology

Boerma, Marjan; Davis, Catherine M.; Jackson, Isabel L.; Schaue, Dörthe; Williams, Jacqueline P.

doi:10.1080/09553002.2021.1941383

Cited by 4 publications

(2 citation statements)

References 294 publications

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“…These data may support that TNF-α alteration was tumor-specific. This finding was supported by a loop between radio-induced inflammation, mobilization of immune cells and sustained tissular damage, mediated by DNA damage and SASP factors following irradiation [ 69 ]. However, our results were in discordance with previous studies that reported persistent systemic inflammation in individuals with a history of IR exposure [ 70 ].…”

Section: Discussionmentioning

confidence: 96%

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma

Jenni

Chikhaoui

Nabouli

et al. 2023

IJMS

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Research in normal tissue radiobiology is in continuous progress to assess cellular response following ionizing radiation exposure especially linked to carcinogenesis risk. This was observed among patients with a history of radiotherapy of the scalp for ringworm who developed basal cell carcinoma (BCC). However, the involved mechanisms remain largely undefined. We performed a gene expression analysis of tumor biopsies and blood of radiation-induced BCC and sporadic patients using reverse transcription-quantitative PCR. Differences across groups were assessed by statistical analysis. Bioinformatic analyses were conducted using miRNet. We showed a significant overexpression of the FOXO3a, ATM, P65, TNF-α and PINK1 genes among radiation-induced BCCs compared to BCCs in sporadic patients. ATM expression level was correlated with FOXO3a. Based on receiver-operating characteristic curves, the differentially expressed genes could significantly discriminate between the two groups. Nevertheless, TNF-α and PINK1 blood expression showed no statistical differences between BCC groups. Bioinformatic analysis revealed that the candidate genes may represent putative targets for microRNAs in the skin. Our findings may yield clues as to the molecular mechanism involved in radiation-induced BCC, suggesting that deregulation of ATM-NF-kB signaling and PINK1 gene expression may contribute to BCC radiation carcinogenesis and that the analyzed genes could represent candidate radiation biomarkers associated with radiation-induced BCC.

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Section: Discussionmentioning

confidence: 96%

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma

Jenni

Chikhaoui

Nabouli

et al. 2023

IJMS

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“…Fibrosis may progress up to 2 years post-exposure after which it generally stabilizes in the lung, although continued lung volume retraction may be observed up to 5 years after exposure. 16 Clinical signs and symptoms of radiation pneumonitis and/ or fibrosis include abnormal pulmonary function tests (e.g., DLCO, diffusing capacity for carbon monoxide; %FEV, percent change in forced expiratory volume), radiographic changes (e.g., ground glass opacification and increased lung density), and microscopic changes (e.g., increased alveolar wall thickness, mononuclear cell infiltration, proteinaceous alveolar, and interstitial edema, as well as collagen deposition and honey-comb scarring).…”

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confidence: 99%

Animal model considerations for medical countermeasure development for radiation and sulfur mustard exposures

Jackson,

Doyle-Eisele

2023

Disaster med. public health prep.

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Development of medical countermeasures (MCM) to mitigate and/or treat the pulmonary complications associated with exposure to chemical, radiological, and/or nuclear weapons is a United States (U.S.) national public health preparedness posture priority. Pulmonary exposure to either sulfur mustard vapor or radiation causes oxidative damage, vascular injury, hyperinflammation, and pro-fibrotic signaling cascades that lead to life-threatening and potentially debilitating lung disease. There is no MCM currently approved by the U.S. Food and Drug Administration (FDA) to mitigate and/or treat lung injury caused by sulfur mustard or radiation exposure. Thus, there remains a major unmet public health need for development of threat-agnostic, host-directed therapeutics that target common pathophysiological mechanisms underlying the progression of acute and/or late lung injury independent of the etiology of disease. This review describes the clinical manifestations and underlying mechanisms of sulfur mustard and radiation-induced lung injury and regulatory considerations for MCM development under the non-traditional Animal Rule pathway.

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A C57L/J Mouse Model of the Delayed Effects of Acute Radiation Exposure in the Context of Evolving Multi-Organ Dysfunction and Failure after Total-Body Irradiation with 2.5% Bone Marrow Sparing

et al. 2023

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The objective of the current study was to establish a mouse model of acute radiation syndrome (ARS) after total-body irradiation with 2.5% bone marrow sparing (TBI/BM2.5) that progressed to the delayed effects of acute radiation exposure, specifically pneumonitis and/or pulmonary fibrosis (DEARE-lung), in animals surviving longer than 60 days. Two hundred age and sex matched C57L/J mice were assigned to one of six arms to receive a dose of 9.5 to 13.25 Gy of 320 kV X-ray TBI/BM2.5. A sham-irradiated cohort was included as an age- and sex-matched control. Blood was sampled from the facial vein prior to irradiation and on days 5, 10, 15, 20, 25, and 30 postirradiation for hematology. Respiratory function was monitored at regular intervals throughout the in-life phase. Animals with respiratory dysfunction were administered a single 12-day tapered regimen of dexamethasone, allometrically scaled from a similar regimen in the non-human primate. All animals were monitored daily for up to 224 days postirradiation for signs of organ dysfunction and morbidity/mortality. At euthanasia due to criteria or at the study endpoint, wet lung weights were recorded, and blood sampled for hematology and serum chemistry. The left lung, heart, spleen, small and large intestine, and kidneys were processed for histopathology. A dose-response curve with the estimated lethal dose for 10–99% of animals with 95% confidence intervals was established. The median survival time was significantly prolonged in males as compared to females across the 10.25 to 12.5 Gy dose range. Animal sex played a significant role in overall survival, with males 50% less likely to expire prior to the study endpoint compared to females. All animals developed pancytopenia within the first one- to two-weeks after TBI/BM2.5 followed by a progressive recovery through day 30. Fourteen percent of animals expired during the first 30-days postirradiation due to ARS (e.g., myelosuppression, gastrointestinal tissue abnormalities), with most deaths occurring prior to day 15. Microscopic findings show the presence of radiation pneumonitis as early as day 57. At time points later than day 70, pneumonitis was consistently present in the lungs of mice and the severity was comparable across radiation dose arms. Pulmonary fibrosis was first noted at day 64 but was not consistently present and stable in severity until after day 70. Fibrosis was comparable across radiation dose arms. In conclusion, this study established a multiple organ injury mouse model that progresses through the ARS phase to DEARE-lung, characterized by respiratory dysfunction, and microscopic abnormalities consistent with radiation pneumonitis/fibrosis. The model provides a platform for future development of medical countermeasures for approval and licensure by the U.S. Food and Drug Administration under the animal rule regulatory pathway.

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All for one, though not one for all: team players in normal tissue radiobiology

Cited by 4 publications

References 294 publications

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma

Differential Expression of ATM, NF-KB, PINK1 and Foxo3a in Radiation-Induced Basal Cell Carcinoma

Animal model considerations for medical countermeasure development for radiation and sulfur mustard exposures

A C57L/J Mouse Model of the Delayed Effects of Acute Radiation Exposure in the Context of Evolving Multi-Organ Dysfunction and Failure after Total-Body Irradiation with 2.5% Bone Marrow Sparing

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