Charged particle mutagenesis at low dose and fluence in mouse splenic T cells

Dmytro Grygoryev, Stacey Gauny, Michael Lasarev, Anna Ohlrich, Amy Kronenberg, Mitchell Turker

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

High-energy heavy charged particles (HZE ions) found in the deep space environment can significantly affect human health by inducing mutations and related cancers. To better understand the relation between HZE ion exposure and somatic mutation, we examined cell survival fraction, Aprt mutant frequencies, and the types of mutations detected for mouse splenic T cells exposed in vivo to graded doses of densely ionizing 48Ti ions (1GeV/amu, LET=107 keV/μm), 56Fe ions (1GeV/amu, LET=151 keV/μm) ions, or sparsely ionizing protons (1GeV, LET=0.24 keV/μm). The lowest doses for 48Ti and 56Fe ions were equivalent to a fluence of approximately 1 or 2 particle traversals per nucleus. In most cases, Aprt mutant frequencies in the irradiated mice were not significantly increased relative to the controls for any of the particles or doses tested at the pre-determined harvest time (3-5 months after irradiation). Despite the lack of increased Aprt mutant frequencies in the irradiated splenocytes, a molecular analysis centered on chromosome 8 revealed the induction of radiation signature mutations (large interstitial deletions and complex mutational patterns), with the highest levels of induction at 2 particles nucleus for the 48Ti and 56Fe ions. In total, the results show that densely ionizing HZE ions can induce characteristic mutations in splenic T cells at low fluence, and that at least a subset of radiation-induced mutant cells are stably retained despite the apparent lack of increased mutant frequencies at the time of harvest.

Original languageEnglish (US)
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
DOIs
Publication statusAccepted/In press - Feb 18 2016

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Keywords

  • Aprt mutation
  • Charged particle mutagenesis
  • Radiation signature mutations
  • Splenic T cells

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis

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