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Space Radiobiology
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Space Radiobiology

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Radiobiology and Nuclear Medicine".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 18462

Special Issue Editors

Dr. Giorgio Russo

E-Mail Website
Guest Editor
Institute of Molecular Bioimaging and Physiology (IBFM), National Research Council (CNR), 90015 Cefalù (PA), Italy
Interests: radiobiology; medical physics; radioprotection; biomedical imaging; cancer biology; tumor hypoxia; radiosensitizing agents; biomarkers; target therapies
Dr. Walter Tinganelli

E-Mail Website
Guest Editor
Biophysics Division, GSI Helmholtz Center for Heavy Ion Research, 64291 Darmstadt, Germany
Interests: space biology; radiobiology; cancer biology; tumor hypoxia; flash radiotherapy; cell and molecular biology; human pathology and physiology; hibernation and synthetic torpor; target therapies
Special Issues, Collections and Topics in MDPI journals
Dr. Marco Calvaruso

E-Mail Website
Guest Editor
National Research Council (CNR), Institute of Bioimaging and Molecular Physiology (IBFM), Cefalù, PA, Italy
Interests: space biology; radiobiology; cancer biology; radiosensitizing agents; cell and molecular biology; tumor immunology; human pathology, immunotherapy; biomarkers; target therapies
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

From the beginning of mankind, humans have always wondered about outer space and conquering it. The first answers to these questions arrived many years later, with the first human in space, launched in 1961, and with the following moon landing in 1969. Since then, the idea to leave our terrestrial shelters, to delve into space and colonize it, has become more and more concrete. However, space is an inhospitable place to explore, and it exposes human travellers to many challenges to their health. In the last 50 years, space biology has enriched the basic knowledge about the effects of space-radiation exposure and gravity unloading. However, the majority of studies have been aimed at the protection of astronauts flying in a low earth orbit (LEO), and they are based on an as yet limited amount of data collected from real space flight conditions or simulated ones.

The steady implementation of space transportation systems, and the future development of the Lunar Gateway, will inevitably lead astronauts to be involved in longer space missions that will be held beyond LEO. Therefore, a deeper elucidation of space-dependent effects related to health risks for the crew represents a major issue. In this context, future studies should not only be aimed at the prevention of health problems in space, but also at the management and resolution of pathological issues that may occur in an altered gravitational environment. It is important to note that these health risks both comprise those deriving from long-term radiation and microgravity exposure (cancer, immunological and neurological impairments, infections, muscle and bone loss, etc), together with those associated with isolation and confinement conditions (psychological problems). On the other hand, outputs coming from space biology research may be useful to ameliorate human life on Earth. 

On these bases, the role of space biology will be pivotal and functional in the future for the prediction, prevention, and management of diseases, and for the development of effective countermeasures to intervene promptly during space missions.

The main goal of this Special Issue is to collect multidisciplinary observations and provide new insights regarding space’s effects on biological systems in order to facilitate human permanence far from terrestrial orbit. Other topics of interest for this Special Issue will be the impact of space biology studies in improving life quality on Earth.

Dr. Marco Calvaruso
Dr. Giorgio Russo
Dr. Walter Tinganelli
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Life is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • radiobiology
  • radioprotection
  • microgravity
  • space radiations
  • DNA damage
  • shielding materials

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Published Papers (6 papers)

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Research

13 pages, 1647 KiB  
Article
Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence
by Polly Y. Chang, James Bakke, Chris J. Rosen, Kathleen A. Bjornstad, Jian-Hua Mao and Eleanor A. Blakely
Life 2022, 12(6), 907; https://doi.org/10.3390/life12060907 - 17 Jun 2022
Cited by 1 | Viewed by 2354
Abstract
There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced [...] Read more.
There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03–0.80 Gy). Female CB6F1 mice were irradiated with low single doses of either oxygen, silicon, titanium, or iron ions at various energies to cover a range of dose-averaged LET values from 0.2–193 keV/µm, using 137Cs γ-rays as the reference radiation. Sham-treated controls were included in each individual experiment totally 398 animals across the 5 studies reported. Based on power calculations, between 40–156 mice were included in each of the treatment groups. Tumor prevalence at 16 months after radiation exposure was determined and compared to the age-matched, sham-treated animals. Results indicate that lung tumor prevalence is non-linear as a function of dose with suggestions of threshold doses depending on the LET of the beams. Histopathological evaluations of the tumors showed that the majority of tumors were benign bronchioloalveolar adenomas with occasional carcinomas or lymphosarcomas which may have resulted from metastases from other sites. Full article
(This article belongs to the Special Issue Space Radiobiology)
►▼ Show Figures

Figure 1

Figure 1
<p>Lung tumor prevalence as a function of dose (<b>top</b>) and particle fluence (<b>bottom</b>). Black symbol (■) represents the spontaneous lung tumor prevalence in sham-treated animals.</p> Full article ">Figure 2
<p>Representative photomicrographs of lung tumor histopathology at necropsy 16 months post irradiation. (<b>A</b>) The yellow arrow points to Broncho-Alveolar Adenoma with adjacent normal tissue from an animal that was irradiated with 0.04 Gy Silicon. (<b>B</b>) Histiocytic Sarcoma in lung tissues from animal exposed to 0.16 Gy Silicon ions.</p> Full article ">Figure 2 Cont.
<p>Representative photomicrographs of lung tumor histopathology at necropsy 16 months post irradiation. (<b>A</b>) The yellow arrow points to Broncho-Alveolar Adenoma with adjacent normal tissue from an animal that was irradiated with 0.04 Gy Silicon. (<b>B</b>) Histiocytic Sarcoma in lung tissues from animal exposed to 0.16 Gy Silicon ions.</p> Full article ">
27 pages, 9665 KiB   250 MeV/n) Ions" data-journal="life">
Article
Impact of Radiation Quality on Microdosimetry and Chromosome Aberrations for High-Energy (>250 MeV/n) Ions
by Floriane Poignant, Ianik Plante, Luis Crespo and Tony Slaba
Life 2022, 12(3), 358; https://doi.org/10.3390/life12030358 - 1 Mar 2022
Cited by 3 | Viewed by 2669
Abstract
Studying energy deposition by space radiation at the cellular scale provides insights on health risks to astronauts. Using the Monte Carlo track structure code RITRACKS, and the chromosome aberrations code RITCARD, we performed a modeling study of single-ion energy deposition spectra and chromosome [...] Read more.
Studying energy deposition by space radiation at the cellular scale provides insights on health risks to astronauts. Using the Monte Carlo track structure code RITRACKS, and the chromosome aberrations code RITCARD, we performed a modeling study of single-ion energy deposition spectra and chromosome aberrations for high-energy (>250 MeV/n) ion beams with linear energy transfer (LET) varying from 0.22 to 149.2 keV/µm. The calculations were performed using cells irradiated directly by mono-energetic ion beams, and by poly-energetic beams after particle transport in a digital mouse model, representing the radiation exposure of a cell in a tissue. To discriminate events from ion tracks directly traversing the nucleus, to events from δ-electrons emitted by distant ion tracks, we categorized ion contributions to microdosimetry or chromosome aberrations into direct and indirect contributions, respectively. The ions were either ions of the mono-energetic beam or secondary ions created in the digital mouse due to interaction of the beam with tissues. For microdosimetry, the indirect contribution is largely independent of the beam LET and minimally impacted by the beam interactions in mice. In contrast, the direct contribution is strongly dependent on the beam LET and shows increased probabilities of having low and high-energy deposition events when considering beam transport. Regarding chromosome aberrations, the indirect contribution induces a small number of simple exchanges, and a negligible number of complex exchanges. The direct contribution is responsible for most simple and complex exchanges. The complex exchanges are significantly increased for some low-LET ion beams when considering beam transport. Full article
(This article belongs to the Special Issue Space Radiobiology)
►▼ Show Figures

Figure 1

Figure 1
<p>Scheme of the geometrical setup for the microdosimetry and chromosome aberration calculations.</p> Full article ">Figure 2
<p>Poly-energetic beam fluence as a function of ion energy after the transport of mono-energetic beams ((<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n) in digital mice, averaged over intra-abdominal organs (bladder, stomach, spleen, pancreas, liver, and kidneys).</p> Full article ">Figure 3
<p>Examples of projected tracks and damages obtained for a dose of 1 Gy, for H 1000 MeV/n (<b>a</b>) + (<b>b</b>), He 250 MeV/n (<b>c</b>) + (<b>d</b>) and C 290 MeV/n (<b>e</b>) + (<b>f</b>). Tracks were clipped to display only energy deposition events inside the nucleus. The direct contribution is displayed in red and the indirect contribution in blue. Simple breaks are represented in green and complex breaks in black. For each beam, the results for mono-energetic (ME) beams are shown on the left ((<b>a</b>,<b>c</b>,<b>e</b>)) and for poly-energetic (PE) beams on the right (<b>b</b>,<b>d</b>,<b>f</b>)).</p> Full article ">Figure 4
<p>Same as <a href="#life-12-00358-f003" class="html-fig">Figure 3</a> but for O 325 MeV/n (<b>a</b>) + (<b>b</b>), Si 300 MeV/n (<b>c</b>) + (<b>d</b>) and Fe 1000 MeV/n (<b>e</b>) + (<b>f</b>).</p> Full article ">Figure 5
<p>Single-ion energy deposition spectra, <span class="html-italic">f</span><sub>tot</sub>(<span class="html-italic">ε</span>), in a spherical target. Results are displayed for 6 incident beams ((<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n), both with (poly-energetic spectra in dashed line) and without (mono-energetic (ME) beam in solid line) beam transport in the Digimouse. <span class="html-italic">f</span><sub>tot</sub>(<span class="html-italic">ε</span>) (in black) is broken down into sub-contributions <span class="html-italic">f</span><sub>dir</sub>(<span class="html-italic">ε</span>) (red) and <span class="html-italic">f</span><sub>ind</sub>(<span class="html-italic">ε</span>) (blue).</p> Full article ">Figure 6
<p>Simple (<b>a</b>–<b>f</b>) and complex (<b>g</b>–<b>l</b>) exchanges per cell for 6 incident beams (H 1000 MeV/n (<b>a</b>) + (<b>g</b>), He 250 MeV/n (<b>b</b>) + (<b>h</b>), C 290 MeV/n (<b>c</b>) + (<b>i</b>), O 325 MeV/n (<b>d</b>) + (<b>j</b>), Si 300 MeV/n (<b>e</b>) + (<b>k</b>) and Fe 1000 MeV/n (<b>f</b>) + (<b>l</b>)). Results are shown without beam transport (mono-energetic beam in solid line + round marker) and with beam transport in the Digimouse (poly-energetic beam in dashed line + diamond marker). The total (black), direct (red), indirect (blue) and direct+indirect (grey) were fitted with a linear quadratic model.</p> Full article ">Figure 7
<p>Average values of the LQ coefficients, <span class="html-italic">μ<sub>α</sub></span> and <span class="html-italic">μ<sub>β</sub></span>, for simple (<b>a</b>,<b>c</b>) and complex (<b>b</b>,<b>d</b>) exchanges as a function of the beam LET, both without beam transport (mono-energetic beam in solid line + round marker) and with beam transport in the Digimouse (poly-energetic spectra in dashed line + diamond marker). Error bars represent the standard deviation, <span class="html-italic">σ<sub>α</sub></span> and <span class="html-italic">σ<sub>β</sub></span>.</p> Full article ">Figure A1
<p>Linear quadratic fit for the dose response for mono-energetic O 325 MeV/n beam and simple exchanges. On the top left (<b>a</b>), dots are the results from RITCARD while the solid line represents the least squares fit, and the dashed line the 95% PI. The marginal PDF of the α and β are plotted on the top right (<b>b</b>) and bottom left (<b>c</b>), while the bottom right (<b>d</b>) shows samples of the joint density.</p> Full article ">Figure A2
<p>Illustration of the PDF, <span class="html-italic">f<sub>y</sub></span> and CDF, <span class="html-italic">F<sub>y</sub></span>, obtained at the dose point <span class="html-italic">D<sub>av</sub></span> = 0.75 Gy, for the contributions <span class="html-italic">i</span> = tot and <span class="html-italic">j</span> = dir + ind, the mono-energetic beam O 325 MeV/n and simple exchanges. The vertical blue line represents the maximum of the difference between <span class="html-italic">F<sub>y</sub></span><sub>,tot</sub> and <span class="html-italic">F<sub>y</sub></span><sub>,dir+ind</sub>.</p> Full article ">Figure A3
<p>Dose–response comparison between the total vs. direct + indirect, for simple exchanges (upper figures). The figures of merit, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>tot</mi> <mo>→</mo> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> <mo>→</mo> <mi>tot</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mrow> <msup> <mi>m</mi> <mo>′</mo> </msup> </mrow> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math>, are plotted in black, red, and blue, respectively (lower figures). The values of the integrals over the dose (Equations (A18)–(A20)), <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>tot</mi> <mo>→</mo> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> <mo>→</mo> <mi>tot</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math> are indicated on each sub-figure. Results are displayed for (<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n.</p> Full article ">Figure A4
<p>Dose–response comparison between the total vs. direct + indirect, for complex exchanges (upper figures). The figures of merit, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>tot</mi> <mo>→</mo> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> <mo>→</mo> <mi>tot</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mrow> <msup> <mi>m</mi> <mo>′</mo> </msup> </mrow> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math>, are plotted in black, red, and blue, respectively (lower figures). The values of the integrals over the dose (Equations (A18)–(A20)), <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>tot</mi> <mo>→</mo> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>dir</mi> <mo>+</mo> <mi>ind</mi> <mo>→</mo> <mi>tot</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math> are indicated on each sub-figure. Results are displayed for (<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n.</p> Full article ">Figure A5
<p>Dose–response comparison between the total contribution obtained for mono-energetic (ME) vs. poly-energetic (PE) beams, for simple exchanges (upper figures). The figures of merit, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>ME</mi> <mo>→</mo> <mi>PE</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>PE</mi> <mo>→</mo> <mi>ME</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mrow> <msup> <mi>m</mi> <mo>′</mo> </msup> </mrow> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math>, are plotted in black, red, and blue, respectively (lower figures). The values of the integrals over the dose (Equations (A18)–(A20)), <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>ME</mi> <mo>→</mo> <mi>PE</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>PE</mi> <mo>→</mo> <mi>ME</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math> are indicated on each sub-figure. Results are display for (<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n.</p> Full article ">Figure A6
<p>Dose–response comparison between the total contribution obtained for mono-energetic (ME) vs. poly-energetic (PE) beams, for complex exchanges (upper figures). The figures of merit, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>ME</mi> <mo>→</mo> <mi>PE</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>P</mi> <mrow> <mi>PE</mi> <mo>→</mo> <mi>ME</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mrow> <msup> <mi>m</mi> <mo>′</mo> </msup> </mrow> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math>, are plotted in black, red, and blue, respectively (lower figures). The values of the integrals over the dose (Equations (A18)–(A20)), <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>ME</mi> <mo>→</mo> <mi>PE</mi> </mrow> </msub> </mrow> </semantics></math>, <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>PE</mi> <mo>→</mo> <mi>ME</mi> </mrow> </msub> </mrow> </semantics></math> and <math display="inline"><semantics> <mrow> <msub> <mi>m</mi> <mrow> <mi>KM</mi> </mrow> </msub> </mrow> </semantics></math> are indicated on each sub-figure. Results are display for (<b>a</b>) H 1000 MeV, (<b>b</b>) He 250 MeV/n, (<b>c</b>) C 290 MeV/n, (<b>d</b>) O 325 MeV/n, (<b>e</b>) Si 300 MeV/n and (<b>f</b>) Fe 1000 MeV/n.</p> Full article ">
18 pages, 3743 KiB  
Article
Response of Arabidopsis thaliana and Mizuna Mustard Seeds to Simulated Space Radiation Exposures
by Ye Zhang, Jeffrey T. Richards, Alan H. Feiveson, Stephanie E. Richards, Srujana Neelam, Thomas W. Dreschel, Ianik Plante, Megumi Hada, Honglu Wu, Gioia D. Massa, Grace L. Douglas and Howard G. Levine
Life 2022, 12(2), 144; https://doi.org/10.3390/life12020144 - 19 Jan 2022
Cited by 9 | Viewed by 3731
Abstract
One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will [...] Read more.
One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is consequences from exposures to solar particle event (SPE) protons and galactic cosmic rays (GCR). For long-term crewed Lunar and Mars explorations, the production of fresh food in space will provide both nutritional supplements and psychological benefits to the astronauts. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of two different compositions of charged particles-simulated GCR, and simulated SPE protons on dry and hydrated seeds of the model plant Arabidopsis thaliana and the crop plant Mizuna mustard [Brassica rapa var. japonica]. Exposures to charged particles, simulated GCRs (up to 80 cGy) or SPEs (up to 200 cGy), were performed either acutely or at a low dose rate using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Control and irradiated seeds were planted in a solid phytogel and grown in a controlled environment. Five to seven days after planting, morphological parameters were measured to evaluate radiation-induced damage in the seedlings. After exposure to single types of charged particles, as well as to simulated GCR, the hydrated Arabidopsis seeds showed dose- and quality-dependent responses, with heavier ions causing more severe defects. Seeds exposed to simulated GCR (dry seeds) and SPE (hydrated seeds) had significant, although much less damage than seeds exposed to heavier and higher linear energy transfer (LET) particles. In general, the extent of damage depends on the seed type. Full article
(This article belongs to the Special Issue Space Radiobiology)
►▼ Show Figures

Figure 1

Figure 1
<p>Particle tracks simulated within the volume of one cell. (<b>A</b>) A single 300 MeV/n Ti particle track with numerous secondary particles within a cell; (<b>B</b>) 250 MeV/n H particle tracks generated within a cell; (<b>C</b>) simulated GCR1 mixed irradiation field within a cell; and (<b>D</b>) simulated GCR2 irradiation field within a cell.</p> Full article ">Figure 2
<p>Effect of 300 MeV/n Ti particles on seed germination, viability, and morphological measurements. (<b>A</b>) Tables of seeds number with percentages of viability, germination, cotyledon deformation, and absence of measurable roots by experimental group. (<b>B</b>) Root length distribution (small circles) in seedlings from control and Ti irradiated seeds. Multiple instances of zero root length are plotted with small jitter so that they can be distinguished. Estimates of 75th percentile root length (orange bars) are shown with 95% confidence limits (dashed lines). (<b>C</b>) Comparative histograms of root-length distributions. (<b>D</b>) Examples of cotyledon deformation. * Indicates <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">Figure 3
<p>Effect of 250 MeV/n protons on root length in seedlings grown from control and irradiated Arabidopsis seeds. (<b>A</b>) <span class="html-italic">Arabidopsis</span> seed number and germination rate. (<b>B</b>) Root length distribution (small circles) in seedlings from control and irradiated seeds. Multiple instances of zero root length, including non-germinated seeds are plotted with small random jitter so that they can be distinguished. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). (<b>C</b>) Comparative histograms of root-length distributions in plants from germinated seeds. * Indicates <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">Figure 4
<p>Effect of GCRs on root length in seedlings from control and irradiated <span class="html-italic">Arabidopsis</span> seeds. (<b>A</b>) <span class="html-italic">Arabidopsis</span> seed number and germination rate. (<b>B</b>) Root length distribution (small circles) in seedlings from control and Ti irradiated seeds. Multiple instances of zero root length (including non-germinated seeds) are plotted with small random jitter so that they can be distinguished. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). (<b>C</b>) Comparative histograms of root-length distributions in plants from germinated seeds.</p> Full article ">Figure 5
<p>The effect of GCR-2 scenario on root length reduction in seedlings developed from control and irradiated dry seeds. (<b>A</b>) <span class="html-italic">Arabidopsis</span> seed number and germination rate. (<b>B</b>) Root length distribution (small circles) in <span class="html-italic">Arabidopsis</span> seedlings from control and irradiated seeds. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. (<b>C</b>) Mizuna seed number and germination rate. (<b>D</b>) Cotyledon deformation rate in Mizuna seedlings. (<b>E</b>) Root length distribution (small circles) in mizuna seedlings from control and irradiated seeds. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. * Shows <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">Figure 6
<p>The effect of SPE scenarios on root length reduction in seedlings developed from control and irradiated imbibed seeds. (<b>A</b>) <span class="html-italic">Arabidopsis</span> seed number and germination rate. (<b>B</b>) Root length distribution (small circles) in <span class="html-italic">Arabidopsis</span> seedlings from control and irradiated seeds. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. (<b>C</b>) Mizuna seed number and germination rate. (<b>D</b>) Cotyledon deformation rate in Mizuna seedlings. (<b>E</b>) Root length distribution (small circles) in mizuna seedlings from control and irradiated seeds. Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). * Indicates <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">Figure 6 Cont.
<p>The effect of SPE scenarios on root length reduction in seedlings developed from control and irradiated imbibed seeds. (<b>A</b>) <span class="html-italic">Arabidopsis</span> seed number and germination rate. (<b>B</b>) Root length distribution (small circles) in <span class="html-italic">Arabidopsis</span> seedlings from control and irradiated seeds. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. (<b>C</b>) Mizuna seed number and germination rate. (<b>D</b>) Cotyledon deformation rate in Mizuna seedlings. (<b>E</b>) Root length distribution (small circles) in mizuna seedlings from control and irradiated seeds. Multiple instances of zero root length (including non-germinated seeds) are plotted with small jitter so that they can be distinguished. Estimates of median root length (orange bars) are shown with 95% confidence limits (dashed lines). * Indicates <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">Figure 7
<p>A plot of estimated ratios (treatment to control) of median root length (proton and CGR) or 75th percentiles (Ti) along with 95% confidence intervals showing that the <span class="html-italic">Arabidopsis</span> seedlings from irradiated seeds generally have shortened root length. Larger uncertainties for Ti exposure reflect the smaller sample size as well as the failure of many seeds to germinate or produce measurable roots. * Indicates <span class="html-italic">p</span> &lt; 0.05 compared to controls.</p> Full article ">
18 pages, 4007 KiB  
Article
Biological and Mechanical Characterization of the Random Positioning Machine (RPM) for Microgravity Simulations
by Marco Calvaruso, Carmelo Militello, Luigi Minafra, Veronica La Regina, Filippo Torrisi, Gaia Pucci, Francesco P. Cammarata, Valentina Bravatà, Giusi I. Forte and Giorgio Russo
Life 2021, 11(11), 1190; https://doi.org/10.3390/life11111190 - 5 Nov 2021
Cited by 14 | Viewed by 2919
Abstract
The rapid improvement of space technologies is leading to the continuous increase of space missions that will soon bring humans back to the Moon and, in the coming future, toward longer interplanetary missions such as the one to Mars. The idea of living [...] Read more.
The rapid improvement of space technologies is leading to the continuous increase of space missions that will soon bring humans back to the Moon and, in the coming future, toward longer interplanetary missions such as the one to Mars. The idea of living in space is charming and fascinating; however, the space environment is a harsh place to host human life and exposes the crew to many physical challenges. The absence of gravity experienced in space affects many aspects of human biology and can be reproduced in vitro with the help of microgravity simulators. Simulated microgravity (s-μg) is applied in many fields of research, ranging from cell biology to physics, including cancer biology. In our study, we aimed to characterize, at the biological and mechanical level, a Random Positioning Machine in order to simulate microgravity in an in vitro model of Triple-Negative Breast Cancer (TNBC). We investigated the effects played by s-μg by analyzing the change of expression of some genes that drive proliferation, survival, cell death, cancer stemness, and metastasis in the human MDA-MB-231 cell line. Besides the mechanical verification of the RPM used in our studies, our biological findings highlighted the impact of s-μg and its putative involvement in cancer progression. Full article
(This article belongs to the Special Issue Space Radiobiology)
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<p>(<b>a</b>) The Random Positioning Machine (RPM) produced by AATC and (<b>b</b>) the RPM operating inside the cell incubator.</p> Full article ">Figure 2
<p>(<b>a</b>) Architectural and (<b>b</b>) functional schemes of the hardware device implemented for rotation measurement.</p> Full article ">Figure 3
<p>(<b>a</b>) Architectural and (<b>b</b>) functional schemes of the hardware device implemented for acceleration measuring.</p> Full article ">Figure 4
<p>Simulated microgravity-induced formation of multicellular spheroids, MCS (red arrows) at 24 and 72 h in MDA-MB-213 cell line; few scattered adherent cells (AD, black arrows). Original magnification 10× and 20×.</p> Full article ">Figure 5
<p>Assessment of cell metabolic activity by means of MTT Cell Viability Assay for AD and the MCS fractions of MDA-MB-231 cell line after 24 and 72 h of microgravity exposure. Data are represented via standard box and whisker plot of <span class="html-italic">n</span> = 3 independent experiments. * <span class="html-italic">p</span>-value &lt; 0.05; **** <span class="html-italic">p</span>-value &lt; 0.0001 (nonparametric Kruskal–Wallis test).</p> Full article ">Figure 6
<p>Results of qRT-PCR for the following genes and main regulated processes: AKT and KI67 (cancer proliferation); BAX and BCL2 (apoptosis); CD44 (cancer stemness), and MMP9 (metastasis). The data shown are relative to the mRNA levels in the MDA-MB-231 control cells at 24 and 72 h. Statistical analysis was performed using the nonparametric Kruskal–Wallis test (* <span class="html-italic">p</span> value &lt; 0.05).</p> Full article ">Figure 7
<p>Example of the periodic trend of the acceleration components along the x, y, and z axes, obtained with the setting (<span class="html-italic">innerRotations</span>, <span class="html-italic">outerRotations</span> = (120, 40) in the ”centered” position (acquired with a 100 Hz sampling frequency).</p> Full article ">
15 pages, 3667 KiB  
Article
Track Structure Components: Characterizing Energy Deposited in Spherical Cells from Direct and Peripheral HZE Ion Hits
by Ianik Plante, Floriane Poignant and Tony Slaba
Life 2021, 11(11), 1112; https://doi.org/10.3390/life11111112 - 20 Oct 2021
Cited by 11 | Viewed by 2285
Abstract
To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and [...] Read more.
To understand the biological effects of radiation, it is important to determine how ionizing radiation deposits energy in micrometric targets. The energy deposited in a target located in an irradiated tissue is a function of several factors such as the radiation type and the irradiated volume size. We simulated the energy deposited by energetic ions in spherical targets of 1, 2, 4, and 8 µm radii encompassed in irradiated parallelepiped volumes of various sizes using the stochastic radiation track structure code Relativistic Ion Tracks (RITRACKS). Because cells are usually part of a tissue when they are irradiated, electrons originating from radiation tracks in neighboring volumes also contribute to energy deposition in the target. To account for this contribution, we used periodic boundary conditions in the simulations. We found that the single-ion spectra of energy deposition in targets comprises two components: the direct ion hits to the targets, which is identical in all irradiation conditions, and the contribution of hits from electrons from neighboring volumes, which depends on the irradiated volume. We also calculated an analytical expression of the indirect hit contributions using the local effect model, which showed results similar to those obtained with RITRACKS. Full article
(This article belongs to the Special Issue Space Radiobiology)
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<p>Scheme of RITRACKS calculations and the definition of direct/indirect contributions (<b>a</b>) and RITRACKS results for an irradiation of a volume by 25 MeV/n carbon ions, without (<b>b</b>) and with (<b>c</b>) PBCs. Using PBCs, it is possible for a delta electron to leave the volume many times; if it is the case, it will reenter as many times as necessary for all its energy to be spent deposited in the simulated volume.</p> Full article ">Figure 2
<p>Predicted and calculated dose to a spherical target encompassed in the center of a cubical volume (2 × 2 × 2 µm) for one incident ion impinging the irradiated surface perpendicularly at a random location. Figures (<b>a</b>) and (<b>b</b>) are identical, but on different scales.</p> Full article ">Figure 3
<p>Comparison of simulation results from RITRACKS calculations and other codes. (<b>a</b>): probability distributions of lineal energy for a 1 µm diameter water sphere irradiated by a single randomly incident proton of 0.3, 0.5, 1.0, 2.0, and 5.0 MeV. The calculations made with RITRACKS (dots) are compared to those published in References [<a href="#B34-life-11-01112" class="html-bibr">34</a>,<a href="#B35-life-11-01112" class="html-bibr">35</a>,<a href="#B36-life-11-01112" class="html-bibr">36</a>,<a href="#B37-life-11-01112" class="html-bibr">37</a>] (lines). (<b>b</b>): Probability distribution of energy deposited in a 1 μm diameter water sphere irradiated by a single randomly incident Ne ion, 46 MeV/n (LET ~133 keV/μm).</p> Full article ">Figure 4
<p>Calculation of energy deposition per track in spherical targets of radius of 1 µm by 1 Gy of 290 MeV/n carbon ions. The irradiation volumes were cubes of different sizes (2, 3, 4, 5, 10, and 20 µm), without PBCs (<b>a</b>) and with PBCs (<b>b</b>).</p> Full article ">Figure 5
<p>Single-ion energy deposition spectra for different ions (1000 MeV protons, 250 MeV/n helium, 290 MeV/n carbon, 325 MeV/n oxygen, 300 MeV/n silicon, and 1000 MeV/n iron ions) and target radii (1, 2, 4, and 8 µm). Contributions: direct (– –), dashed (- - -), total (⋅ ⋅ ⋅). Due to the large differences between the direct and indirect contributions at almost all energies, the total contributions overlap with the direct or indirect contribution, whichever is largest.</p> Full article ">Figure 6
<p>Scaling of the energy distribution spectra. (<b>a</b>) direct energy distribution spectra of all ions (1000 MeV protons, 250 MeV/n helium, 290 MeV/n carbon, 325 MeV/n oxygen, 300 MeV/n silicon, and 1000 MeV/n iron ions) and target sizes (1, 2, 4, and 8 µm), normalized to the LET and radius in the energy axis, and to LET<sup>2</sup> and radius in the frequency axis. (<b>b</b>) indirect energy distribution spectra, normalized to the target radius.</p> Full article ">Figure 7
<p>Comparison of analytical calculations using the LEM and results from RITRACKS simulations. (<b>a</b>) radial dose for a carbon ion, 290 MeV/n, calculated by RITRACKS, the LEM (Equation (3)) and the LEM with a factor 0.5 applied. (<b>b</b>) dose to spherical targets as a function of the impact parameter for one single 290 MeV/n carbon track (dots), and LEM prediction (lines), for targets of radius 0.5, 1, and 2 μm. (<b>c</b>) calculations of indirect dose in targets of radius 1, 2, and 3 μm, calculated by RITRACKS (dots) and compared with analytical LEM calculations (lines). For this simulation, a disk surface of radius rm was irradiated uniformly by 290 MeV/n carbon tracks. For the LEM results, a radial dose multiplicative factor of 0.5 was applied. The calculations were conducted without PBC.</p> Full article ">Figure 8
<p>Ejected electron energy spectra for all ions, normalized to the LET. The peak at 500 eV corresponds to Auger electrons that are ejected when an internal orbital of the water molecule is ionized.</p> Full article ">
14 pages, 3001 KiB  
Article
Evaluating Ocular Response in the Retina and Optic Nerve Head after Single and Fractionated High-Energy Protons
by Xiao-Wen Mao, Seta Stanbouly, Tamako Jones and Gregory Nelson
Life 2021, 11(8), 849; https://doi.org/10.3390/life11080849 - 19 Aug 2021
Cited by 3 | Viewed by 2583
Abstract
There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and [...] Read more.
There are serious concerns about possible late radiation damage to ocular tissue from prolonged space radiation exposure, and occupational and medical procedures. This study aimed to investigate the effects of whole-body high-energy proton exposure at a single dose on apoptosis, oxidative stress, and blood-retina barrier (BRB) integrity in the retina and optic nerve head (ONH) region and to compare these radiation-induced effects with those produced by fractionated dose. Six-month-old C57BL/6 male mice were either sham irradiated or received whole-body high energy proton irradiation at an acute single dose of 0.5 Gy or 12 equal dose fractions for a total dose of 0.5 Gy over twenty-five days. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. Significant increases in the number of apoptotic cells were documented in the mouse retinas and ONHs that received proton radiation with a single or fractionated dose (p < 0.05). Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina and ONH following single or fractionated protons with more pronounced changes observed with a single dose of 0.5 Gy. BRB integrity was also evaluated with biomarkers of aquaporin-4 (AQP-4), a water channel protein, a tight junction (TJ) protein, Zonula occludens-1 (ZO-1), and an adhesion molecule, the platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following a single dose exposure compared to controls. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina. These changes give a strong indication of disturbance to BRB integrity in the retina. Interestingly, there was very limited immunoreactivity of AQP-4 and ZO-1 seen in the ONH region, pointing to possible lack of BRB properties as previously reported. Our data demonstrated that exposure to proton radiation of 0.5 Gy induced oxidative stress-associated apoptosis in the retina and ONH, and changes in BRB integrity in the retina. Our study also revealed the differences in BRB biomarker distribution between these two regions. In response to radiation insults, the cellular response in the retina and ONH may be differentially regulated in acute or hyperfractionated dose schedules. Full article
(This article belongs to the Special Issue Space Radiobiology)
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<p>Apoptosis based on terminal deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL) staining of male C57BL/6 following an acute single or fractionated (12 equal fractions) proton irradiation for a total dose of 0.5 Gy in mouse ocular tissue. (<b>A</b>) Apoptotic cell density in the retinal outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL); (<b>B</b>) Apoptotic cell density in the optic nerve head (ONH) region. The density profiles were expressed as the mean number of apoptotic positive cells/mm<sup>2</sup>. The mean of the density profile measurements across 5 retina sections per eye was used as one experimental value. Values are represented as mean density ± SEM for 6 mice/group. <sup>a</sup> Significantly higher than controls (<span class="html-italic">p</span> &lt; 0.05). <sup>b</sup> Significantly higher than all other groups (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 2
<p>Cellular oxidative damage in the retina and optic nerve head (ONH). (<b>A</b>) Representative micrographs of ocular sections were evaluated for lipid peroxidation by immunostaining with anti-4-hydroxynonenal (4-HNE) antibody in the retina of irradiated and control samples. 4-HNE positive staining was identified with red fluorescence; the nuclei were counterstained with DAPI (blue). The vessels were stained with tomato lectin (green). Scale bar = 50 μm. (<b>B</b>) The average fluorescence intensity for HNE in the retina was measured and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean density ± SEM for 6 mice/group. <sup>a</sup> Significantly increased 4-HNE staining compared to control group (<span class="html-italic">p</span> &lt; 0.05). <sup>†</sup> Higher than control with a strong trend (<span class="html-italic">p =</span> 0.06). (<b>C</b>) Representative micrographs of ocular sections were evaluated for lipid peroxidation by immunostaining with anti-4-hydroxynonenal (4-HNE) antibody in the ONH. (<b>D</b>) The average fluorescence intensity for HNE in the ONH was measured and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean fluorescence intensity ± SEM for 6 mice/group. <sup>a</sup> Significantly higher than all other groups (<span class="html-italic">p</span> &lt; 0.05). <sup>b</sup> Significantly higher than the control group (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 2 Cont.
<p>Cellular oxidative damage in the retina and optic nerve head (ONH). (<b>A</b>) Representative micrographs of ocular sections were evaluated for lipid peroxidation by immunostaining with anti-4-hydroxynonenal (4-HNE) antibody in the retina of irradiated and control samples. 4-HNE positive staining was identified with red fluorescence; the nuclei were counterstained with DAPI (blue). The vessels were stained with tomato lectin (green). Scale bar = 50 μm. (<b>B</b>) The average fluorescence intensity for HNE in the retina was measured and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean density ± SEM for 6 mice/group. <sup>a</sup> Significantly increased 4-HNE staining compared to control group (<span class="html-italic">p</span> &lt; 0.05). <sup>†</sup> Higher than control with a strong trend (<span class="html-italic">p =</span> 0.06). (<b>C</b>) Representative micrographs of ocular sections were evaluated for lipid peroxidation by immunostaining with anti-4-hydroxynonenal (4-HNE) antibody in the ONH. (<b>D</b>) The average fluorescence intensity for HNE in the ONH was measured and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean fluorescence intensity ± SEM for 6 mice/group. <sup>a</sup> Significantly higher than all other groups (<span class="html-italic">p</span> &lt; 0.05). <sup>b</sup> Significantly higher than the control group (<span class="html-italic">p</span> &lt; 0.05).</p> Full article ">Figure 3
<p>Glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP-4) staining in the retina and ONH. (<b>A</b>) Representative micrographs of ocular sections with anti-GFAP and AQP-4 antibodies in the retina of irradiated and control samples. AQP-4 positive staining is identified by green fluorescence, GFAP with red, and the cell nuclei with blue (DAPI). Scale bar = 50 μm. (<b>B</b>) The average fluorescence intensity for AQP-4 was measured in the retina and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean fluorescence intensity ± SEM for 5–6 mice/group. <sup>a</sup> Significantly higher than control group (<span class="html-italic">p</span> &lt; 0.05). <sup>†</sup> Higher than controls with a strong trend (<span class="html-italic">p =</span> 0.07).</p> Full article ">Figure 4
<p>Platelet endothelial cell adhesion molecule (PECAM-1) staining in the retina and ONH. (<b>A</b>) Representative images of PECAM-1 ocular sections in the retina of proton irradiated and control mice. PECAM-1 positive cells were identified with red fluorescence, endothelium was stained with lectin (green). The nuclei of photoreceptors were counterstained with DAPI (blue). Scale bar = 50 μm. (<b>B</b>) Immunoreactivity of PECAM-1 staining in the retina. The average fluorescence intensity for PECAM-1 activity was measured and calculated using the ImageJ program. Fluorescence was averaged across 5 ocular sections per eye as one experimental value. Values are represented as mean fluorescence intensity ± SEM for 5–6 mice/group. <sup>a</sup> Significantly higher than controls in the retina (<span class="html-italic">p</span> &lt; 0.05). (<b>C</b>) Representative images of PECAM-1 ocular sections in the retina of proton irradiated and control mice. <sup>a</sup> Significantly higher than control group in the ONH (<span class="html-italic">p &lt;</span> 0.05).</p> Full article ">Figure 5
<p>Zonula occludens-1 (ZO-1) staining in the retina and ONH. (<b>A</b>) Representative images of ZO-1 in ocular sections of proton irradiated and control mice. ZO-1 positive cells were identified with red fluorescence, endothelium was stained with lectin (green). The nuclei of photoreceptors were counterstained with DAPI (blue). Scale bar = 50 μm. (<b>B</b>) Immunoreactivity of ZO-1 staining in the retina. The average fluorescence intensity for ZO-1 was measured and calculated using the ImageJ program. Fluorescence was averaged across five retinas per group as one experimental value. Values are represented as mean fluorescence intensity ± SEM for 5–6 mice/group. <sup>a</sup> Significantly higher than other groups (<span class="html-italic">p &lt;</span> 0.05).</p> Full article ">
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