Skip to main content
Log in

Frozen human cells can record radiation damage accumulated during space flight: mutation induction and radioadaptation

  • Original Paper
  • Published:
Radiation and Environmental Biophysics Aims and scope Submit manuscript

Abstract

To estimate the space-radiation effects separately from other space-environmental effects such as microgravity, frozen human lymphoblastoid TK6 cells were sent to the “Kibo” module of the International Space Station (ISS), preserved under frozen condition during the mission and finally recovered to Earth (after a total of 134 days flight, 72 mSv). Biological assays were performed on the cells recovered to Earth. We observed a tendency of increase (2.3-fold) in thymidine kinase deficient (TK) mutations over the ground control. Loss of heterozygosity (LOH) analysis on the mutants also demonstrated a tendency of increase in proportion of the large deletion (beyond the TK locus) events, 6/41 in the in-flight samples and 1/17 in the ground control. Furthermore, in-flight samples exhibited 48% of the ground-control level in TK mutation frequency upon exposure to a subsequent 2 Gy dose of X-rays, suggesting a tendency of radioadaptation when compared with the ground-control samples. The tendency of radioadaptation was also supported by the post-flight assays on DNA double-strand break repair: a 1.8- and 1.7-fold higher efficiency of in-flight samples compared to ground control via non-homologous end-joining and homologous recombination, respectively. These observations suggest that this system can be used as a biodosimeter, because DNA damage generated by space radiation is considered to be accumulated in the cells preserved frozen during the mission, Furthermore, this system is also suggested to be applicable for evaluating various cellular responses to low-dose space radiation, providing a better understanding of biological space-radiation effects as well as estimation of health influences of future space explores.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Cramer P, Atanasova P, Vrolijk H, Darroudi B, van Zeeland AA, Huiskamp R, Mullenders LH, Kleinjans JC (2005) Pre exposure to low doses: modulation of X-ray induced DNA damage and repair? Radiat Res 164:383–390

    Article  Google Scholar 

  • Cucinotta FA, Durante M (2006) Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol 7:431–435

    Article  Google Scholar 

  • Cucinotta FA, Kim NH, Willingham V, George KA (2008) Physical and biological organ dosimetry analysis for international space station astronauts. Radiat Res 170:127–138

    Article  Google Scholar 

  • Durante M, Cucinotta FA (2008) Heavy ion carcinogenesis and human space exploration. Nat Rev Cancer 8:465–472

    Article  Google Scholar 

  • Durante M, Reitz G, Angerer O (2010) Space radiation research in Europe: flight experiments and ground-based studies. Radiat Environ Biophys 49:295–302

    Article  Google Scholar 

  • Dziegielewski J, Goetz W, Baulch JE (2010) Heavy ions, radioprotectors and genomic instability: implications for human space exploration. Radiat Environ Biophys 49:303–316

    Article  Google Scholar 

  • ESA (2003) HUMEX: Study in survivability and adaptation of humans to long-duration interplanetary and planetary environments. ESA-ESTEC/SP-1264

  • Fedorenko B, Druzhinin S, Yudaeva L, Petrov V, Akatov Y, Snigiryova G, Novitskaya N, Shevchenko V, Rubanovich A (2001) Cytogenic studies of blood lymphocytes from cosmonauts after long-term space flights on Mir station. Adv Space Res 27:355–359

    Article  ADS  Google Scholar 

  • Fukuda T, Fukuda K, Takahashi A, Ohnishi T, Nakano T, Sato M, Gunge N (2000) Analysis of deletion mutations of the rpsL gene in the yeast Saccharomyces cerevisiae detected after long-term flight on the Russian space station Mir. Mutat Res 470:125–132

    Google Scholar 

  • George K, Willingham V, Cucinotta FA (2005) Stability of chromosome aberrations in the blood lymphocytes of astronauts measured after space flight by FISH chromosome painting. Radiat Res 166:474–480

    Article  Google Scholar 

  • Greco O, Durante M, Gialanella G, Grossi G, Pugliese M, Scampoli P, Snigiryova G, Obe G (2003) Biological dosimetry in Russian and Italian astronauts. Adv Space Res 31:1495–1503

    Article  ADS  Google Scholar 

  • Harada K, Sugahara T, Ohnishi T, Ozaki Y, Obiya Y, Miki S, Miki T, Imamura M, Kobayashi K, Watanabe H, Akashi M, Furusawa Y, Mizuma M, Yamanaka H, Ohashi E, Yamaoka C, Yajima M, Fukui M, Nakano T, Takahashi S, Amano T, Sekikawa K, Yanagawa K, Nagaoka S (1988) Inhibition in a microgravity environment of the recovery Escherichia coli cells damaged by heavy-ion beams during the NASDA ISS Phase I Program of Shuttle/Mission No. 6. Int J Mol Med 1:817–822

    Google Scholar 

  • Held KD (2009) Effects of low fluences of radiations found in space on cellular systems. Int J Radiat Biol 85:379–390

    Article  Google Scholar 

  • Honma M, Izumi M, Sakuraba M, Tadokoro S, Sakamoto H, Wang W, Yatagai F, Hayashi M (2003) Deletion, rearrangement, and gene conversion; genetic consequences of chromosomal double-strand breaks in human cells. Environ Mol Mutagen 42:288–298

    Article  Google Scholar 

  • Ikenaga M, Yoshikawa I, Kojo M, Ayaki T, Ryo H, Ishizaki K, Kato T, Yamamoto H, Hara R (1997) Mutations induced in Drosophila during space flight. Biol Sci Space 11:346–450

    Article  Google Scholar 

  • Ikushima T, Aritomi H, Morisita J (1996) Radioadaptive response: efficient repair of radiation- induced DNA damage in adapted cells. Mutat Res 358:193–198

    Article  Google Scholar 

  • JDX-2009905 (2009) http://idb.exst.jaxa.jp/db_data/padles/S001.php?locale=ja

  • Kim M-HY, Cucinotta FA, Wilson JW (2007) A temporal forecast of radiation environments for future space exploration missions. Radiat Environ Biophys 46:95–100

    Google Scholar 

  • Kobayashi Y, Kikuchi M, Nagaoka S, Watanabe H (1996) Recovery of Deinococcus radiodurans from radiation damage was enhanced under microgravity. Biol Sci Space 10:97–101

    Article  Google Scholar 

  • Morimoto S, Kato T, Honma M, Hayashi M, Hanaoka F, Yatagai F (2002a) Detection of genetic alterations induced by low-dose X rays: analysis of loss of heterozygosity for TK mutation in human lymphoblastoid cells. Radiat Res 157:533–538

    Article  Google Scholar 

  • Morimoto S, Honma M, Yatagai F (2002b) Sensitive detection of LOH events in a human cell line after C-ion beam exposure. J Radiat Res 43(suppl):S163–S167

    Article  Google Scholar 

  • National Academy of Sciences (2006) Space studies board. Space radiation hazards and the vision for space exploration

  • National Academy Press NASA (2009) Human Health and Performance Risks for Space Exploration Missions. NASA-SP-2009-3405, Houston, TX

  • NCRP (2006) Information needed to make radiation protection recommendations for space missions beyond low-earth orbit. Report No. 153. Bethesda, MD, USA, 2006

  • Obe G, Johannes I, Johannes C, Hallman K, Reitz G, Facius R (1997) Chromosomal aberrations in blood lymphocytes of astronauts after long-term space flights. Int J Radiat Biol 72:727–734

    Article  Google Scholar 

  • Ohnishi T, Takahashi A, Wang X, Ohnishi K, Ohira Y, Nagaoka S (1999) Accumulation of a tumor suppressor p53 protein in rat muscle during a space flight. Mutat Res 430:271–274

    Article  Google Scholar 

  • Pross HD, Kiefer J (1999) Repair of cellular radiation damage in space under microgravity conditions. Radiat Environ Biophys 38:133–138

    Article  Google Scholar 

  • Pugliese M, Bengin V, Casolino M, Roca V, Zanini A, Durante M (2010) Tests of shielding effectiveness of Kevlar and Nextel onboard the international space station (ISS) and the FOTON-M3capsule. Radiat Environ Biophys 49:359–363

    Article  Google Scholar 

  • Reitz G, Beaujean R, Benton E, Burmeister S, Dachev Ts, Deme S, Luszik-Bhadra M, Olkop (2005) Space radiation measurements onboard ISS-the DOSMAP experiment. Radiat Prot Dosim 116:374–379

    Article  Google Scholar 

  • Rigaud O, Papadopoulo D, Moustacchi E (1996) Decreased deletion mutation in radioadapted human lymphoblast. Radiat Res 133:94–101

    Article  Google Scholar 

  • Schimmerling W (2010) Accepting space radiation risks. Radiat Environ Biophys 49:325–329

    Article  Google Scholar 

  • Szumiel I (2005) Adaptive responses: stimulated DNA repair or decreased damage fixation? Int J Radiat Biol 81:233–241

    Article  Google Scholar 

  • Takahashi A, Ohnishi K, Takahashi S, Masukawa M, Sekikawa K, Amano T, Nakano T, Nagaoka S, Ohnishi T (2000) The effects of microgravity on ligase activity in the repair of DNA double-strand breaks. Int J Radiat Biol 76:783–788

    Article  Google Scholar 

  • Umebayashi Y, Honma M, Abe T, Ryuto H, Suzuki H, Shimazu T, Ishioka N, Iwaki M, Yatagai F (2005) Mutation induction after low-dose carbon-ion beam irradiation of frozen human cultured cells. Biol Sci Space 19:237–241

    Article  Google Scholar 

  • Umebayashi Y, Honma M, Suzuki M, Suzuki H, Shimazu T, Ishioka N, Iwaki M, Yatagai F (2007) Mutation induction in cultured human cells after low-dose and low-dose rate γ-rays: detection by LOH analysis. J Radiat Res 48:7–11

    Article  Google Scholar 

  • UNSCEAR 1993 Report, (1993) Appendix A, Table 28 (p. 81)

  • White RJ, Averner M (2001) Humans in space. Nature 409:1115–1118

    Article  ADS  Google Scholar 

  • Yang TC, George K, Johnson AS, Durante M, Fedorenko BS (1997) Biodosimetry results from space flight Mir-18. Radiat Res 148:S17–S23

    Google Scholar 

  • Yatagai F, Saito T, Takahashi A, Fujie A, Nagaoka S, Sato M, Ohnishi T (2000) rpsL mutation induction after space flight on MIR. Mutat Res 453:1–4

    Article  Google Scholar 

  • Yatagai F, Morimoto S, Kato T, Honma M (2004) Further characterization of loss of heterozygosity enhanced by p53 abrogation in human lymphoblastoid TK6 cells: disappearance of endpoint hotspots. Mutat Res 560:133–145

    Google Scholar 

  • Yatagai F, Umebayashi Y, Honma M, Sugasawa K, Takayama Y, Hanaoka F (2008a) Mutagenic radioadaptation in a human lymphoblastoid cell line. Mutat Res 638:48–55

    Article  Google Scholar 

  • Yatagai F, Suzuki M, Ishioka N, Omori H, Honma M (2008b) Repair of I-SceI induced DSB at a specific site of chromosome in human cells: influence of low-dose, low-dose rate gamma-rays. Radiat Environ Biophys 47:439–444

    Article  Google Scholar 

  • Yatagai F, Sugasawa K, Enomoto S, Honma M (2009a) An approach to estimate radioadaptation from DSB repair efficiency. J Radiat Res 50:407–413

    Article  Google Scholar 

  • Yatagai F, Takahashi A, Honma M, Suzuki H, Omori K, Seki M, Hashizume T, Shimazu T, Enomoto S, Ohnishi T, Ishioka N (2009b) LOH analyses for biological effects of space radiation: human cell culture in “Kibo” of international space station. Biol Sci Space 23:11–16

    Article  Google Scholar 

  • Yu X, Wang H, Wang P, Chen BPC (2010) The ku-dependent non-homologous end-joining pathway contributes to low dose radiation-stimulated cell survival. J Cell Physiol (July 27 online)

Download references

Acknowledgments

The authors greatly appreciate Dr. Aiko Nagamatsu of JAXA for radiation dosimetry. They also express a deep appreciation to staff of JAXA, Japan Space Forum and JAMASS for supporting this ISS experiment.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fumio Yatagai.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yatagai, F., Honma, M., Takahashi, A. et al. Frozen human cells can record radiation damage accumulated during space flight: mutation induction and radioadaptation. Radiat Environ Biophys 50, 125–134 (2011). https://doi.org/10.1007/s00411-010-0348-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00411-010-0348-3

Keywords

Navigation