title: Frozen human cells can record radiation damage accumulated during space flight: mutation induction and radioadaptation.
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.
authors.affiliation: The Institute of Physical and Chemical Research (RIKEN), Saitama, 351-0198, Japan. yatagai@riken.jp
authors.forename: Fumio
authors.initials: F
authors.lastname: Yatagai
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Honma
authors.forename: Akihisa
authors.initials: A
authors.lastname: Takahashi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Omori
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Toru
authors.initials: T
authors.lastname: Shimazu
authors.forename: Masaya
authors.initials: M
authors.lastname: Seki
authors.forename: Toko
authors.initials: T
authors.lastname: Hashizume
authors.forename: Akiko
authors.initials: A
authors.lastname: Ukai
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.forename: Tomoko
authors.initials: T
authors.lastname: Abe
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Shuichi
authors.initials: S
authors.lastname: Enomoto
authors.forename: Takeo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Alasdair
authors.initials: A
authors.lastname: Gordon
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ishioka
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects*; D002460:Cell Line; D015925:Cryopreservation / Q000379:methods*; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D004781:Environmental Exposure / Q000009:adverse effects; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism / Q000528:radiation effects; D009154:Mutation / Q000528:radiation effects*; D011832:Radiation Injuries / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D011874:Radiometry; D013026:Space Flight; D013937:Thymidine Kinase / Q000235:genetics; D014965:X-Rays
chemical_list: D013937:Thymidine Kinase; D015252:Deoxyribonucleases, Type II Site-Specific