Age dependence of radiation-induced genomic instability in mouse hematopoietic stem cells

Kentaro Ariyoshi, Tomisato Miura, Kosuke Kasai, Nakata Akifumi, Yohei Fujishima, Mayumi Shinagawa, Kyoko Kadono, Mayumi Nishimura, Shizuko Kakinuma, Mitsuaki A. Yoshida

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Age at exposure is a critical factor that influences the risk of radiation-induced leukemia. Accumulating evidence suggests that ionizing radiation can induce genomic instability and promote leukemogenesis in hematopoietic stem cells (HSCs); however, the influence of age on this phenomenon has not been elucidated. In this study, infant (1-week-old) or adult (14-week-old) C3H/He mice received sham or 4 Gy whole-body irradiation, and bone marrow cells were transplanted to recipients at day 1 or 60 postirradiation. Twelve days after bone marrow transplant, we analyzed the radiation-induced genomic instability by scoring the frequency of DNA damage and micronucleus formation in colony-forming units-spleen (CFU-Ss). We observed significant increases in DNA damage and micronucleus formation in CFU-Ss of the 4 Gy irradiated adult cells transplanted at day 1 or 60 postirradiation. However, the frequency of DNA damage focus and micronucleus formation in CFU-Ss of 4 Gy irradiated infant cells transplanted at day 1 or 60 postirradiation was relatively decreased. Quantitative differences in the reactive oxygen species and cells expressing inducible nitric oxide synthase in CFU-Ss suggested that age-dependent radiation-induced genomic instability may result from chronic oxidative stress by pro-inflammatory states in HSC descendants after radiation exposure.

Original languageEnglish
Pages (from-to)623-633
Number of pages11
JournalRadiation Research
Volume190
Issue number6
DOIs
Publication statusPublished - 2018 Dec 1
Externally publishedYes

ASJC Scopus subject areas

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

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