Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change

Mitchell Turker, Dmytro Grygoryev, Michael Lasarev, Anna Ohlrich, Furaha A. Rwatambuga, Sorrel Johnson, Cristian Dan, Bradley Eckelmann, Gwen Hryciw, Jian Hua Mao, Antoine M. Snijders, Stacey Gauny, Amy Kronenberg

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Abstract

Exposure to a small number of high-energy heavy charged particles (HZE ions), as found in the deep space environment, could significantly affect astronaut health following prolonged periods of space travel if these ions induce mutations and related cancers. In this study, we used an in vivo mutagenesis assay to define the mutagenic effects of accelerated 56Fe ions (1 GeV/amu, 151 keV/μm) in the mouse kidney epithelium exposed to doses ranging from 0.25 to 2.0 Gy. These doses represent fluences ranging from 1 to 8 particle traversals per cell nucleus. The Aprt locus, located on chromosome 8, was used to select induced and spontaneous mutants. To fully define the mutagenic effects, we used multiple endpoints including mutant frequencies, mutation spectrum for chromosome 8, translocations involving chromosome 8, and mutations affecting non-selected chromosomes. The results demonstrate mutagenic effects that often affect multiple chromosomes for all Fe ion doses tested. For comparison with the most abundant sparsely ionizing particle found in space, we also examined the mutagenic effects of high-energy protons (1 GeV, 0.24 keV/μm) at 0.5 and 1.0 Gy. Similar doses of protons were not as mutagenic as Fe ions for many assays, though genomic effects were detected in Aprt mutants at these doses. Considered as a whole, the data demonstrate that Fe ions are highly mutagenic at the low doses and fluences of relevance to human spaceflight, and that cells with considerable genomic mutations are readily induced by these exposures and persist in the kidney epithelium. The level of genomic change produced by low fluence exposure to heavy ions is reminiscent of the extensive rearrangements seen in tumor genomes suggesting a potential initiation step in radiation carcinogenesis.

Original languageEnglish (US)
Article numbere0180412
JournalPLoS One
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2017

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Chromosomes
kidneys
Ions
Radiation
ions
Kidney
genomics
Chromosomes, Human, Pair 8
mutants
mice
dosage
chromosomes
mutation
Mutation
Protons
Assays
protons
Epithelium
Cosmic Radiation
Astronauts

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Turker, M., Grygoryev, D., Lasarev, M., Ohlrich, A., Rwatambuga, F. A., Johnson, S., ... Kronenberg, A. (2017). Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change. PLoS One, 12(7), [e0180412]. https://doi.org/10.1371/journal.pone.0180412

Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change. / Turker, Mitchell; Grygoryev, Dmytro; Lasarev, Michael; Ohlrich, Anna; Rwatambuga, Furaha A.; Johnson, Sorrel; Dan, Cristian; Eckelmann, Bradley; Hryciw, Gwen; Mao, Jian Hua; Snijders, Antoine M.; Gauny, Stacey; Kronenberg, Amy.

In: PLoS One, Vol. 12, No. 7, e0180412, 01.07.2017.

Research output: Contribution to journalArticle

Turker, M, Grygoryev, D, Lasarev, M, Ohlrich, A, Rwatambuga, FA, Johnson, S, Dan, C, Eckelmann, B, Hryciw, G, Mao, JH, Snijders, AM, Gauny, S & Kronenberg, A 2017, 'Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change', PLoS One, vol. 12, no. 7, e0180412. https://doi.org/10.1371/journal.pone.0180412
Turker, Mitchell ; Grygoryev, Dmytro ; Lasarev, Michael ; Ohlrich, Anna ; Rwatambuga, Furaha A. ; Johnson, Sorrel ; Dan, Cristian ; Eckelmann, Bradley ; Hryciw, Gwen ; Mao, Jian Hua ; Snijders, Antoine M. ; Gauny, Stacey ; Kronenberg, Amy. / Simulated space radiation-induced mutants in the mouse kidney display widespread genomic change. In: PLoS One. 2017 ; Vol. 12, No. 7.
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