Damage to Mouse Lung with Fractionated Neutrons and X Rays

Hornsey, Shirley; Kutsutani, Y.; Sb, Field

doi:10.1148/116.1.171

Cited by 42 publications

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“…6 ). Detailed characteristics of the 13 studies included are provided (Additional file 1 : Table S1) [ 15 , 16 , 21 , 22 , 29 – 37 ]. The value of α/β ratio may vary with different functional assays, endpoints, follow-up time and biophysical models.…”

Section: Resultsmentioning

confidence: 99%

Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model

et al. 2017

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BackgroundNormal lung tissue tolerance constitutes a limiting factor in delivering the required dose of radiotherapy to cure thoracic and chest wall malignancies. Radiation-induced lung fibrosis (RILF) is considered a critical determinant for late normal tissue complications. While RILF mouse models are frequently approached e.g., as a single high dose thoracic irradiation to investigate lung fibrosis and candidate modulators, a systematic radiobiological characterization of RILF mouse model is urgently needed to compare relative biological effectiveness (RBE) of particle irradiation with protons, helium-, carbon and oxygen ions now available at HIT. We aimed to study the dose-response relationship and fractionation effect of photon irradiation in development of pulmonary fibrosis in C57BL/6 mouse.MethodsLung fibrosis was evaluated 24 weeks after single and fractionated whole thoracic irradiation by quantitative assessment of lung alterations using CT. The fibrosis index (FI) was determined based on 3D-segmentation of the lungs considering the two key fibrosis parameters affected by ionizing radiation i.e., a dose/fractionation dependent reduction of the total lung volume and increase of the mean lung density.ResultsThe effective dose required to induce 50% of the maximal possible fibrosis (ED 50) was 14.55 ± 0.34Gy and 27.7 ± 1.22Gy, for single and five- fractions irradiation, respectively. Applying a deterministic model an α/β = 4.49 ± 0.38 Gy for the late lung radiosensitivity was determined. Intriguingly, we found that a linear-quadratic model could be applied to in-vivo log transformed fibrosis (FI) vs. irradiation doses. The LQ model revealed an α/β for lung radiosensitivity of 4.4879 Gy for single fraction and 3.9474 for 5-fractions. Our FI based data were in good agreement with a meta-analysis of previous lung radiosensitivity data derived from different clinical endpoints and various mouse strains. The effect of fractionation on RILF development was further estimated by the biologically effective dose (BED) model with threshold BED (BED Tr) = 30.33 Gy and BED ED50 = 61.63 Gy, respectively.ConclusionThe systematic radiobiological characterization of RILF in the C57BL/6 mouse reported in this study marks an important step towards precise estimation of dose-response for development of lung fibrosis. These radiobiological parameters combined with a large repertoire of genetically engineered C57BL/6 mouse models, build a solid foundation for further biologically individualized risk assessment of RILF and functional RBE prediction on novel of particle qualities.Electronic supplementary materialThe online version of this article (10.1186/s13014-017-0912-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model

et al. 2017

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“…Chronic late developing injuries considered by Barendsen [6] include those for D ⊗ equal to the dose that produces 50 percent death of mice by 180 days from respiratory failure [3] , [23] , [24] ; D ⊗ equal to the dose causing 50 percent death by 180 days from kidney failure [25] ; D ⊗ equal to the dose that produces 30 percent contraction of mouse skin by 250 days [26] ; D ⊗ equal to the dose that produces paralysis of the hind legs of 50 percent of rats from radiation myelopathy of the spinal cord [27] , [28] , [29] ; and 50 percent death of rats by one year from brain irradiation [30] . Like that for the acute early injuries there is a suggestion of downward concavity of the iso effect relation.…”

Section: Discussion: Normal Tissuesmentioning

confidence: 99%

Effect of heterogeneous radio sensitivity on the survival, alpha beta ratio and biologic effective dose calculation of irradiated mammalian cell populations

Hawkins

2017

Clinical and Translational Radiation Oncology

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It is demonstrated that the surviving fraction of a population of cells with heterogeneous radio sensitivity, like that composing most malignant tumors, conforms to a different linear quadratic survival relation for dose less than about 3–5 Gy and dose greater than about 7–9 Gy. In the intermediate range of dose the survival relation for the population, as a whole, is not linear quadratic. Consequently, the value of the alpha beta ratio and the associated biologically effective dose calculation are different for the low and high dose range for most malignant tumors.Normal tissue cell populations responsible for organ function also have heterogeneous radio sensitivity, though to less degree than most malignant tumors. Consequently, the alpha beta ratio and associated biologically effective dose calculation related to the development of some acute early and chronic late developing radiation injuries are not the same in the low and high dose range.Variance of the distribution of α of a heterogeneous cell population lowers the effective value of the quadratic survival constant β of the population, as a whole, and increases the α/β ratio in the low dose range. Heterogeneous appearance of tumor cells (pleomorphism) and necrosis on biopsy or imaging studies reflect heterogeneity of the radio sensitivity of the cells. Greater heterogeneity implies a tendency to higher α/β ratio. This may furnish a clinically accessible way to estimate a value of the α/β ratio specific to an individual patient and tumor.

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“…1). Tikvah Alper cooperated with Shirley Hornsey who was a very productive scientist working on radiation injury in mouse lung, 10 spinal cord, 11 jejunum, 12 RBE of fast neutrons, 13 and hypoxia. Her most remarkable achievement was obtained in cooperation with Hal Gray.…”

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confidence: 99%

The contribution of women to radiobiology: Marie Curie and beyond

Gasińska

2016

Reports of Practical Oncology & Radiotherapy

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Radiobiology Ionizing radiationTumor radiobiology a b s t r a c t Marie Sklodowska-Curie, an extraordinary woman, a Polish scientist who lived and worked in France, led to the development of nuclear energy and the treatment of cancer. She was the laureate of two Nobel Prizes, the first woman in Europe who obtained the degree of Doctor of Science and opened the way for women to enter fields which had been previously reserved for men only. As a result of her determination and her love of freedom, she has become an icon for many female scientists active in radiation sciences. In 1911, Marie Sklodowska-Curie was awarded her second Nobel Prize for the discovery of radium. Her pioneering work demonstrated that radiation is a powerful tool with a wide range of potential applications, which include a range of diagnostic and therapeutic medical procedures. Marie Curie has left a great deal to the world. Her work led to the development http://dx

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Damage to Mouse Lung with Fractionated Neutrons and X Rays

Cited by 42 publications

References 0 publications

Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model

Quantitative assessment of radiation dose and fractionation effects on normal tissue by utilizing a novel lung fibrosis index model

Effect of heterogeneous radio sensitivity on the survival, alpha beta ratio and biologic effective dose calculation of irradiated mammalian cell populations

The contribution of women to radiobiology: Marie Curie and beyond

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