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Predominant contribution of the dose received from constituent heavy-ions in the induction of gastrointestinal tumorigenesis after simulated space radiation exposure

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Abstract

Gastrointestinal (GI) cancer risk among astronauts after encountering galactic cosmic radiation (GCR) is predicted to exceed safe permissible limits in long duration deep-space missions. Current predictions are based on relative biological effectiveness (RBE) values derived from in-vivo studies using single-ion beams, while GCR is essentially a mixed radiation field composed of protons (H), helium (He), and heavy ions. Therefore, a sequentially delivered proton (H) → Helium (He) → Oxygen (O) → Silicon (Si) beam was designed to simulate simplified-mixed-field GCR (Smf-GCR), and Apc1638N/+ mice were total-body irradiated to sham or γ (157Cs) or Smf-GCR followed by assessment of GI-tumorigenesis at 150 days post-exposure. Further, GI-tumor data from equivalent doses of heavy-ions (i.e., 0.05 Gy of O and Si) in 0.5 Gy of Smf-GCR were compared to understand the contributions of heavy-ions in GI-tumorigenesis. The Smf-GCR-induced tumor and carcinoma count were significantly greater than γ-rays, and male preponderance for GI-tumorigenesis was consistent with our earlier findings. Comparison of tumor data from Smf-GCR and equivalent doses of heavy ions revealed an association between higher GI-tumorigenesis where dose received from heavy-ions contributed to > 95% of the total GI-tumorigenic effect observed after Smf-GCR. This study provides the first experimental evidence that cancer risk after GCR exposure could largely depend on doses received from constituent heavy-ions.

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Acknowledgements

We are thankful to the National Aeronautics and Space Administration (NASA) for funding this study through grant# NNX09AU95G and 80NSSC22K1279. We highly appreciate the outstanding support provided by Dr. Adam Rusek, Dr. Peter Guida, and all the staff members of the NASA Space Radiation Laboratory (NSRL) to conduct space radiation exposures. We also acknowledge Ms. Ake Pelagie for animal colony maintenance.

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Authors and Affiliations

  1. Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Research Building, Room E504, 3970 Reservoir Rd., NW, Washington, DC, 20057, USA

    Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Jerry Angdisen, Kamal Datta & Albert J. Fornace Jr.

  2. Department of Pathology, Georgetown University Medical Center, Washington, DC, 20057, USA

    Bhaskar V. S. Kallakury

  3. Department of Biochemistry and Molecular and Cellular Biology and Department of Oncology, Georgetown University Medical Center, Washington, DC, 20057, USA

    Kamal Datta & Albert J. Fornace Jr.

Authors
  1. Shubhankar Suman
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  2. Santosh Kumar
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  3. Bhaskar V. S. Kallakury
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  4. Bo-Hyun Moon
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  5. Jerry Angdisen
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  6. Kamal Datta
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  7. Albert J. Fornace Jr.
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Contributions

SS, KD, and AF designed the study; SS, BK, KD, SK, BM, and JA performed the experiments; SS wrote the manuscript and incorporated inputs from all the co-authors.

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Correspondence to Shubhankar Suman.

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Suman, S., Kumar, S., Kallakury, B.V.S. et al. Predominant contribution of the dose received from constituent heavy-ions in the induction of gastrointestinal tumorigenesis after simulated space radiation exposure. Radiat Environ Biophys 61, 631–637 (2022). https://doi.org/10.1007/s00411-022-00997-z

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  • DOI: https://doi.org/10.1007/s00411-022-00997-z

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