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Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.

ABSTRACT: PURPOSE:Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation. MATERIALS AND METHODS:Male C57BL/6?J mice were exposed to oxygen ions (16O, 600 MeV/n at 0.25-0.26?Gy/min to a total dose of 0, 0.05, 0.1, 0.25, or 1?Gy), protons (150 MeV, 0.35-0.55?Gy/min to 0, 0.5, or 1?Gy), or protons (150 MeV, 0.5?Gy) followed by 16O (600 MeV/n, 0.1?Gy). Separate groups of mice received 137Cs ?-rays (1?Gy/min to 0, 0.5, 1, or 3?Gy) as a reference. Cardiac function and blood velocity were measured with ultrasonography at 3, 5, 7, and 9 months after irradiation. At 2 weeks, 3 months, and 9 months, cardiac tissue was collected to assess apoptosis, tissue remodeling, and markers of immune cells. RESULTS:Ejection fraction and fractional shortening decreased at 3 and 7 months after 16O. These parameters did not change in mice exposed to ?-rays, protons, or protons followed by 16O. Each of the radiation exposures caused only small increases in cleaved caspase-3 and numbers of apoptotic nuclei. Changes in the levels of ?-smooth muscle cell actin and a 75-kDa peptide of collagen type III in the left ventricle suggested tissue remodeling, but there was no significant change in total collagen deposition at 2 weeks, 3 months, and 9 months. Increases in protein amounts of cluster of differentiation (CD)2, CD68, and CD45 as measured with immunoblots at 2 weeks, 3 months, and 9 months after exposure to protons or 16O alone suggested immune cell infiltration. For type III collagen, CD2 and CD68, the efficacy in inducing protein abundance of CD2, CD68, and CD45 was 16O > protons > ?-rays > protons followed by 16O. CONCLUSIONS:Low-dose, high-energy charged-particle irradiation caused mild changes in cardiac function and tissue remodeling in the mouse.

SUBMITTER: Seawright JW

PROVIDER: S-EPMC6391741 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.

Seawright John W JW Sridharan Vijayalakshmi V Landes Reid D RD Cao Maohua M Singh Preeti P Koturbash Igor I Mao Xiao-Wen XW Miousse Isabelle R IR Singh Sharda P SP Nelson Gregory A GA Hauer-Jensen Martin M Boerma Marjan M

Life sciences in space research 20190115

<h4>Purpose</h4>Astronauts traveling beyond low-Earth orbit will be exposed to high linear-energy transfer charged particles. Because there is concern about the adverse effects of space radiation on the cardiovascular system, this study assessed cardiac function and structure and immune cell infiltration in a mouse model of charged-particle irradiation.<h4>Materials and methods</h4>Male C57BL/6 J mice were exposed to oxygen ions (<sup>16</sup>O, 600 MeV/n at 0.25-0.26 Gy/min to a total dose of 0 ...[more]

PMID: 30797436

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Project description:PurposeStudies are required to determine whether exposures to radiation encountered during manned missions in deep space may have adverse effects on the cardiovascular system. Most of the prior studies on effects of simulated space radiation on the heart and vasculature have been performed in mouse models. To provide data from a second animal species, two studies were performed to assess effects of high-energy charged particle radiation on the heart and abdominal aorta in a rat model.Materials and methodsIn study A, male Long Evans rats were exposed to whole-body protons (250 MeV, 0.5 Gy) or oxygen ions (16O, 600 MeV/n, 0.5 Gy), and ultrasonography was used to measure in vivo cardiac function and blood flow parameters at 3, 5, 9 and 12 months after radiation, followed by tissue collection at 12 months. In study B, male Long Evans rats were exposed to 16O (1 GeV/n, 0.01-0.25 Gy), and hearts collected at 6 to 7 and 12 months for histology and western-blots.ResultsBoth protons (250 MeV) and 16O (600 MeV/n) caused a decrease in left ventricular posterior wall thickness at 3-5 months, but did not change echocardiographic measures of cardiac function. In Pulsed-wave Doppler assessment of the abdominal aorta, an increase was seen in mean velocity, peak velocity, and velocity time integral at 12 months after 16O (600 MeV/n), suggesting a change in vascular function. There were no significant changes in histopathology or histological quantification of total collagens in heart or aorta. On the other hand, an increase was seen in a 75 kDa peptide of collagen type III in the left ventricle of rats exposed to protons (250 MeV) and 16O (600 MeV/n and 1 GeV/n), suggesting that radiation caused remodeling of existing collagens in the heart. 16O (600 MeV/n and 1 GeV/n) caused increases in left ventricular protein levels of immune cell markers CD2, CD4, CD8, and CD68.ConclusionA single low dose of whole body protons or 16O in male Long Evans rats did not change cardiac function or induce gross pathological changes in the heart or aorta, but induced mild changes in vascular function and remodeling of existing collagens in the heart. Altogether, studies in prior mouse models and the current work in rats indicate minor changes in cardiac function and structure after a low dose of single-ion radiation.

Project description:PurposeThis work presents the validation of an analytical pencil beam dose calculation algorithm in a commercial treatment planning system (TPS) for carbon ions by measurements of dose distributions in heterogeneous phantom geometries. Additionally, a comparison study of carbon ions versus protons is performed considering current best solutions in commercial TPS.MethodsAll treatment plans were optimized and calculated using the RayStation TPS (RaySearch, Sweden). The dose distributions calculated with the TPS were compared with measurements using a 24-pinpoint ionization chamber array (T31015, PTW, Germany). Tissue-like inhomogeneities (bone, lung, and soft tissue) were embedded in water, while a target volume of 4 x 4 x 4 cm3 was defined at two different depths behind the heterogeneities. In total, 10 different test cases, with and without range shifter as well as different air gaps, were investigated. Dose distributions inside as well as behind the target volume were evaluated.ResultsInside the target volume, the mean dose difference between calculations and measurements, averaged over all test cases, was 1.6% for carbon ions. This compares well to the final agreement of 1.5% obtained in water at the commissioning stage of the TPS for carbon ions and is also within the clinically acceptable interval of 3%. The mean dose difference and maximal dose difference obtained outside the target area were 1.8% and 13.4%, respectively. The agreement of dose distributions for carbon ions in the target volumes was comparable or better to that between Monte Carlo (MC) dose calculations and measurements for protons. Percentage dose differences of more than 10% were present outside the target area behind bone-lung structures, where the carbon ion calculations systematically over predicted the dose. MC dose calculations for protons were superior to carbon ion beams outside the target volumes.ConclusionThe pencil beam dose calculations for carbon ions in RayStation were found to be in good agreement with dosimetric measurements in heterogeneous geometries for points of interest located within the target. Large local discrepancies behind the target may contribute to incorrect dose predictions for organs at risk.

Dataset Information

Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.

Publications

Effects of low-dose oxygen ions and protons on cardiac function and structure in male C57BL/6J mice.

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