Accelerated 48Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence

Gwen Hryciw, Dmytro Grygoryev, Michael Lasarev, Anna Ohlrich, Cristian Dan, Ravi Madhira, Bradley Eckelmann, Stacey Gauny, Amy Kronenberg, Mitchell Turker

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Exposure to high-energy charged particles (HZE ions) at low fluence could significantly affect astronaut health after prolonged missions in deep space by inducing mutations and related cancers. We tested the hypothesis that the mutagenic effects of HZE ions could be detected at low fluence in a mouse model that detects autosomal mutations in vivo. Aprt heterozygous mice were exposed to 0.2, 0.4 and 1.4 Gy of densely ionizing 48Ti ions (1 GeV/amu, LET = 107 keV/μm). We observed a dose-dependent increase in the Aprt mutant fraction in kidney epithelium at the two lowest doses (an average of 1 or 2 particles/cell nucleus) that plateaued at the highest dose (7 particles/cell nucleus). Mutant cells were expanded to determine mutation spectra and translocations affecting chromosome 8, which encodes Aprt. A PCR-based analysis for loss of heterozygosity (LOH) events on chromosome 8 demonstrated a significant shift in the mutational spectrum from Ti ion exposure, even at low fluence, by revealing "radiation signature" mutations in mutant cells from exposed mice. Likewise, a cytogenetic assay for nonreciprocal chromosome 8 translocations showed an effect of exposure. A genome-wide LOH assay for events affecting nonselected chromosomes also showed an effect of exposure even for the lowest dose tested. Considered in their entirety, these results show that accelerated 48Ti ions induce large mutations affecting one or more chromosomes at low dose and fluence.

Original languageEnglish (US)
Pages (from-to)367-377
Number of pages11
JournalRadiation Research
Volume184
Issue number4
DOIs
StatePublished - Oct 1 2015

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epithelium
chromosomes
kidneys
mutations
mice
fluence
Epithelium
Chromosomes, Human, Pair 8
Ions
Kidney
dosage
Mutation
Loss of Heterozygosity
ions
Cell Nucleus
Cosmic Radiation
Chromosomes
Astronauts
Linear Energy Transfer
astronauts

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Accelerated 48Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence. / Hryciw, Gwen; Grygoryev, Dmytro; Lasarev, Michael; Ohlrich, Anna; Dan, Cristian; Madhira, Ravi; Eckelmann, Bradley; Gauny, Stacey; Kronenberg, Amy; Turker, Mitchell.

In: Radiation Research, Vol. 184, No. 4, 01.10.2015, p. 367-377.

Research output: Contribution to journalArticle

Hryciw, G, Grygoryev, D, Lasarev, M, Ohlrich, A, Dan, C, Madhira, R, Eckelmann, B, Gauny, S, Kronenberg, A & Turker, M 2015, 'Accelerated 48Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence', Radiation Research, vol. 184, no. 4, pp. 367-377. https://doi.org/10.1667/RR14130.1
Hryciw G, Grygoryev D, Lasarev M, Ohlrich A, Dan C, Madhira R et al. Accelerated 48Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence. Radiation Research. 2015 Oct 1;184(4):367-377. https://doi.org/10.1667/RR14130.1
Hryciw, Gwen ; Grygoryev, Dmytro ; Lasarev, Michael ; Ohlrich, Anna ; Dan, Cristian ; Madhira, Ravi ; Eckelmann, Bradley ; Gauny, Stacey ; Kronenberg, Amy ; Turker, Mitchell. / Accelerated 48Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence. In: Radiation Research. 2015 ; Vol. 184, No. 4. pp. 367-377.
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