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Predicting chromosome damage in astronauts participating in international space station missions.

ABSTRACT: Space radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether individual radiosensitivity, as determined by the ex vivo dose-response of the pre-flight chromosome aberration rate (CAR), contributes to the prediction of the post-flight CAR incurred from the radiation exposure during missions. Random-effects Poisson regression was used to estimate subject-specific radiosensitivities from the preflight dose-response data, which were in turn used to predict post-flight CAR and subject-specific relative biological effectiveness (RBEs) between space radiation and gamma radiation. Covariates age, gender were also considered. Results indicate that there is predictive value in background CAR as well as radiosensitivity determined preflight for explaining individual differences in post-flight CAR over and above that which could be explained by BFO dose alone. The in vivo RBE for space radiation was estimated to be approximately 3 relative to the ex vivo dose response to gamma irradiation. In addition, pre-flight radiosensitivity tended to be higher for individuals having a higher background CAR, suggesting that individuals with greater radiosensitivity can be more sensitive to other environmental stressors encountered in daily life. We also noted that both background CAR and radiosensitivity tend to increase with age, although both are highly variable. Finally, we observed no significant difference between the observed CAR shortly after mission and at?>?6 months post-mission.

SUBMITTER: Feiveson A

PROVIDER: S-EPMC7935859 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Predicting chromosome damage in astronauts participating in international space station missions.

Feiveson Alan A George Kerry K Shavers Mark M Moreno-Villanueva Maria M Zhang Ye Y Babiak-Vazquez Adriana A Crucian Brian B Semones Edward E Wu Honglu H

Scientific reports 20210305 1

Space radiation consists of energetic protons and other heavier ions. During the International Space Station program, chromosome aberrations in lymphocytes of astronauts have been analyzed to estimate received biological doses of space radiation. More specifically, pre-flight blood samples were exposed ex vivo to varying doses of gamma rays, while post-flight blood samples were collected shortly and several months after landing. Here, in a study of 43 crew-missions, we investigated whether indiv ...[more]

PMID: 33674665

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Project description:IntroductionSpaceflight leads to the deconditioning of multiple body systems including the immune system. We sought to characterize the molecular response involved by capturing changes in leukocyte transcriptomes from astronauts transitioning to and from long-duration spaceflight.MethodsFourteen male and female astronauts with ~6-month- long missions aboard the International Space Station (ISS) had 10 blood samples collected throughout the three phases of the study: one pre-flight (PF), four in-flight (IF) while onboard the ISS, and five upon return to Earth (R). We measured gene expression through RNA sequencing of leukocytes and applied generalized linear modeling to assess differential expression across all 10 time points followed by the analysis of selected time points and functional enrichment of changing genes to identify shifts in biological processes.ResultsOur temporal analysis identified 276 differentially expressed transcripts grouped into two clusters (C) showing opposite profiles of expression with transitions to and from spaceflight: (C1) decrease-then-increase and (C2) increase-then-decrease. Both clusters converged toward average expression between ~2 and ~6 months in space. Further analysis of spaceflight transitions identified the decrease-then-increase pattern with most changes: 112 downregulated genes between PF and early spaceflight and 135 upregulated genes between late IF and R. Interestingly, 100 genes were both downregulated when reaching space and upregulated when landing on Earth. Functional enrichment at the transition to space related to immune suppression increased cell housekeeping functions and reduced cell proliferation. In contrast, egress to Earth is related to immune reactivation.ConclusionThe leukocytes' transcriptome changes describe rapid adaptations in response to entering space followed by opposite changes upon returning to Earth. These results shed light on immune modulation in space and highlight the major adaptive changes in cellular activity engaged to adapt to extreme environments.

Project description:STUDY DESIGN:Prospective case series. OBJECTIVE:Evaluate lumbar paraspinal muscle (PSM) cross-sectional area and intervertebral disc (IVD) height changes induced by a 6-month space mission on the International Space Station. The long-term objective of this project is to promote spine health and prevent spinal injury during space missions and here on Earth. SUMMARY OF BACKGROUND DATA:National Aeronautics and Space Administration (NASA) crewmembers have a 4.3 times higher risk of herniated IVDs, compared with the general and military aviator populations. The highest risk occurs during the first year after a mission. Microgravity exposure during long-duration spaceflights results in approximately 5 cm lengthening of body height, spinal pain, and skeletal deconditioning. How the PSMs and IVDs respond during spaceflight is not well described. METHODS:Six NASA crewmembers were imaged supine with a 3 Tesla magnetic resonance imaging. Imaging was conducted preflight, immediately postflight, and then 33 to 67 days after landing. Functional cross-sectional area (FCSA) measurements of the PSMs were performed at the L3-4 level. FCSA was measured by grayscale thresholding within the posterior lumbar extensors to isolate lean muscle on T2-weighted scans. IVD heights were measured at the anterior, middle, and posterior sections of all lumbar levels. Repeated measures analysis of variance was used to determine significance at P?<?0.05, followed by post-hoc testing. RESULTS:Paraspinal lean muscle mass, as indicated by the FCSA, decreased from 86% of the total PSM cross-sectional area down to 72%, immediately after the mission. Recovery of 68% of the postflight loss occurred during the next 6 weeks, still leaving a significantly lower lean muscle fractional content compared with preflight values. In contrast, lumbar IVD heights were not appreciably different at any time point. CONCLUSION:The data reveal lumbar spine PSM atrophy after long-duration spaceflight. Some FCSA recovery was seen with 46 days postflight in a terrestrial environment, but it remained incomplete compared with preflight levels. LEVEL OF EVIDENCE:4.

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Predicting chromosome damage in astronauts participating in international space station missions.

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Predicting chromosome damage in astronauts participating in international space station missions.

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