Chromosome aberrations in normal human fibroblasts analyzed in G0/G1 and G2/M phases after exposure in G0 to radiation with different linear energy transfer (LET)

Cuihua Liu, Tetsuya Kawata, Yoshiya Furusawa, Guangming Zhou, Kohei Inoue, Junichi Fukada, Ryuichi Kota, Kerry George, Francis Cucinotta, Ryuichi Okayasu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We have studied the induction of chromosome aberrations in human fibroblasts exposed in G0/G1 to X-rays or heavy ions to study the influence of G1 cell cycle arrest. Confluent normal fibroblasts were exposed to X-rays or accelerated particles with different LET values and chromosome aberrations were investigated in the first G0/G1 and G2//M phase. The particles used here were 490MeV/nucleon Si, 500MeV/nucleon Fe, and 200MeV/nucleon Fe ions. Cells were subcultured 24h after exposure and premature chromosome condensation (PCC) was performed by fusion-induced method for analysis of G0/G1 cells, and chemically-induced method for analysis of G2 and metaphase cells. Chromosome damage was assessed in chromosomes 1 and 3 using whole chromosome fluorescence in situ hybridization (FISH). Cell cycle was analyzed by flow cytometry at different incubation times following subculture. After irradiation with 2Gy of high-LET particles, the yields of chromosome aberrations and fragments were significantly higher in G0/G1 phase than in G2/M phase, whereas similar yields of damage were measured in both phases after exposure to X-rays. In contrast, the yield of misrepair, assessed by the number of color junctions, was similar in the G0/G1 and G2/M phases after exposure to either X-rays or high-LET particles. The yields of chromosome aberrations, fragments, and color junctions in both the G0/G1 and the G2/M phases, increased with LET up to 200keV/μm, then decreased for 440keV/μm Fe particles. A good correlation was found between chromosome aberrations in both G0/G1 and G2/M cells and survival fractions after 2Gy of different LET radiations, although the slopes were steeper for the G0/G1 cells. Flow cytometry analysis indicated that high-LET particles induce more non cycling G0/G1 cells within 48h of subculture than X-rays, suggesting that chromosome aberrations scored at the G2/M phase may not accurately describe the true radiation effect.

Original languageEnglish
Pages (from-to)101-107
Number of pages7
JournalMutation Research - Genetic Toxicology and Environmental Mutagenesis
Volume756
Issue number1-2
DOIs
Publication statusPublished - 2013 May 30

Keywords

  • Cell cycle arrest
  • Chromosome aberration
  • Fluorescence in situ hybridization (FISH)
  • High-LET radiation
  • Premature chromosome condensation (PCC)

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

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