Effect of radiation dose rate and cyclophosphamide on pulmonary toxicity after total body irradiation in a mouse model

Safwat, Akmal; Nielsen, Ole Steen; El-Badawy, Samy; Overgaard, Jens

doi:10.1016/0360-3016(95)02078-0

Cited by 15 publications

(13 citation statements)

References 19 publications

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“…2C) exposures. The genes with a greater response to acute exposures echo the protective effect of exposure protraction reported for end points from cell mutation (42) to short- and long-term survival of mice (13–15). We have also investigated physiological responses in peripheral blood cells in mice exposed to the same doses and dose rates that were used here for gene expression studies (43).…”

Section: Discussionmentioning

confidence: 62%

“…As protraction of an exposure over time can significantly decrease the extent of injury compared with an acute dose (12), understanding the rate of exposure could be very important for triage and selection of the most appropriate treatment. For instance, protraction of dose rate has been shown to increase the LD 50 for both acute and late radiation syndromes in several mouse strains (13–15). Current biodosimetry approaches, however, have not been developed to distinguish between acute and LDR exposures for assessment of potential radiological injury.…”

Section: Introductionmentioning

confidence: 99%

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Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

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In the event of a nuclear accident or radiological terrorist attack, there will be a pressing need for biodosimetry to triage a large, potentially exposed population and to assign individuals to appropriate treatment. Exposures from fallout are likely, resulting in protracted dose delivery that would, in turn, impact the extent of injury. Biodosimetry approaches that can distinguish such low-dose-rate (LDR) exposures from acute exposures have not yet been developed. In this study, we used the C57BL/6 mouse model in an initial investigation of the impact of low-dose-rate delivery on the transcriptomic response in blood. While a large number of the same genes responded to LDR and acute radiation exposures, for many genes the magnitude of response was lower after LDR exposures. Some genes, however, were differentially expressed (P < 0.001, false discovery rate < 5%) in mice exposed to LDR compared with mice exposed to acute radiation. We identified a set of 164 genes that correctly classified 97% of the samples in this experiment as exposed to acute or LDR radiation using a support vector machine algorithm. Gene expression is a promising approach to radiation biodosimetry, enhanced greatly by this first demonstration of its potential for distinguishing between acute and LDR exposures. Further development of this aspect of radiation biodosimetry, either as part of a complete gene expression biodosimetry test or as an adjunct to other methods, could provide vital triage information in a mass radiological casualty event.

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Section: Discussionmentioning

confidence: 62%

Section: Introductionmentioning

confidence: 99%

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

et al. 2015

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“…Adverse effects of irradiating the thorax include lung fibrosis, pneumonitis, and neoplasia, although previous studies have shown that mice are able to survive these complications following up to 20 repeated radiation exposures of a similar X-ray dose to the imaging studies reported here (48). In addition, the lethal dose to 50% of the population for all types of lung damage in mice is reported to be between 9 and 12 Gy, which is much higher than the dose received during the imaging procedure (14,53). However, some disease models may be affected by the radiation dose received during scanning; further investigation of the effect of the X-ray dose in longitudinal imaging is needed to ensure that the disease progression or treatment is not affected by the imaging techniques used.…”

Section: Discussionmentioning

confidence: 70%

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography

Ford¹,

Martin²,

Lewis³

et al. 2007

Journal of Applied Physiology

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Lung morphology and function in human subjects can be monitored with computed tomography (CT). Because many human respiratory diseases are routinely modeled in rodents, a means of monitoring the changes in the structure and function of the rodent lung is desired. High-resolution images of the rodent lung can be attained with specialized micro-CT equipment, which provides a means of monitoring rodent models of lung disease noninvasively with a clinically relevant method. Previous studies have shown respiratory-gated images of intubated and respirated mice. Although the image quality and resolution are sufficient in these studies to make quantitative measurements, these measurements of lung structure will depend on the settings of the ventilator and not on the respiratory mechanics of the individual animals. In addition, intubation and ventilation can have unnatural effects on the respiratory dynamics of the animal, because the airway pressure, tidal volume, and respiratory rate are selected by the operator. In these experiments, important information about the symptoms of the respiratory disease being studied may be missed because the respiration is forced to conform to the ventilator settings. In this study, we implement a method of respiratory-gated micro-CT for use with anesthetized free-breathing rodents. From the micro-CT images, quantitative analysis of the structure of the lungs of healthy unconscious mice was performed to obtain airway diameters, lung and airway volumes, and CT densities at end expiration and during inspiration. Because the animals were free breathing, we were able to calculate tidal volume (0.09 +/- 0.03 ml) and functional residual capacity (0.16 +/- 0.03 ml).

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“…Also, one retrospective study found that using a TBI dose rate of less than 4 cGy/min was significantly associated with reducing the incidence of interstitial pneumonitis [ 21 ]. Furthermore, in a mouse model for BMT, a high TBI dose rate was more toxic than a low dose rate, assessed by a lethal dose for 50% mortality and ventilation rate [ 24 ]. However, all these studies were the results of TBI settings that were delivered twice-daily.…”

Section: Discussionmentioning

confidence: 99%

Effect of dose rate on pulmonary toxicity in patients with hematolymphoid malignancies undergoing total body irradiation

Kim

Yoon

et al. 2018

Radiat Oncol

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BackgroundThis study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation.MethodsThe incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy-seven patients receiving once-daily TBI between 2000 and 2016 were reviewed. We compared the cumulative rate of PT, overall survival (OS), relapse, and transplantation-related mortality (TRM) between conventional (n = 54) and reduced (n = 23) groups. Factors associated with PT were assessed in the presence of competing risks.ResultsThe median follow-up time was 40.7 months, and PT occurred in 50 patients (64.9%). On multivariate analyses, the groups classified by the dose rate (P = 0.010), total dose (P = 0.025), and conditioning regimen (P = 0.029) were significant factors for the development of PT. OS was significantly reduced when PT occurred (P < 0.001). However, the OS, relapse, and TRM were not different between the two groups.ConclusionsIn summary, about two-thirds of the patients undergoing daily TBI experienced PT, which affected OS. Therefore, reducing the dose rate (less than 6 cGy/min) of TBI can decrease the risk of PT, without compromising the treatment efficacy.

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Effect of radiation dose rate and cyclophosphamide on pulmonary toxicity after total body irradiation in a mouse model

Cited by 15 publications

References 19 publications

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

Radiation Dose-Rate Effects on Gene Expression in a Mouse Biodosimetry Model

In vivo characterization of lung morphology and function in anesthetized free-breathing mice using micro-computed tomography

Effect of dose rate on pulmonary toxicity in patients with hematolymphoid malignancies undergoing total body irradiation

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