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Title: Irradiation at Different Fetal Stages Results in Different Translocation Frequencies in Adult Mouse Thyroid Cells

While it is generally believed that fetuses are at high risk of developing cancers, including leukemia, after low doses of radiation, it has been reported that atomic bomb survivors exposed in utero did not show a dose response for translocations in blood T lymphocytes when they were examined at approximately 40 years of age. Subsequent mouse studies confirmed that animals irradiated during the fetal stage did not show evidence of radiation effects in lymphocytes and bone marrow cells when they were examined after reaching adulthood. However, in a study of rat mammary epithelial cells, radiation effects were clearly observed after fetal irradiation. These results indicate that the fate of chromosome aberrations induced in a fetus could vary among different tissues. Here we report on translocation frequencies in mouse thyroid cells, which were irradiated at different stages of fetal development. Cytogenetic examination was then conducted using fluorescence in situ hybridization (FISH) painting of chromosomes 1 and 3. Adult mice, 2 Gy X-ray irradiated at 15.5-day-old fetuses (E15.5), showed a higher translocation frequency (30/1,155 or 25.3 x 10 -3) than nonirradiated adult controls (0/1,007 or 0.1 x 10 -3), and was near that experienced by irradiated mothers and non-pregnant adult females (43/1,244more » or 33.7 x 10 -3). These results are consistent with those seen in rat mammary cells. However, when fetuses were irradiated at an earlier stage of development (E6.5) before thyroid organogenesis, the resulting observed translocation frequency was much lower (3/502 or 5.8 x 10 -3) than that in E15.5 mice. These results suggest that after fetal irradiation, tissue stem cells record radiation effects primarily when the exposure occurs in cells that have been integrated into tissue. Embryonic stem cells that have been damaged prior to integration into the niche may undergo negative selection due to apoptosis, mitotic death or stem cell-niche cell interactions. The implications of these results in interpreting cancer risks after fetal irradiation are also discussed.« less
Authors:
 [1] ;  [2] ;  [1] ;  [1] ;  [1]
  1. Radiation Effects Research Foundation (RERF), Hiroshima (Japan). Dept. of Molecular Biosciences
  2. Radiation Effects Research Foundation (RERF), Hiroshima (Japan). Dept. of Statistics; Univ. of Arkansas for Medical Sciences, Little Rock, AR (United States). Dept. of Biostatistics
Publication Date:
Grant/Contract Number:
HS0000031; 24710067
Type:
Accepted Manuscript
Journal Name:
Radiation Research
Additional Journal Information:
Journal Volume: 186; Journal Issue: 4; Journal ID: ISSN 0033-7587
Publisher:
Radiation Research Society
Research Org:
National Academy of Sciences (NAS), Washington, DC (United States)
Sponsoring Org:
USDOE; Japanese Ministry of Health, Labor and Welfare (MHLW); Radiation Effects Research Foundation (RERF); Japan Society for the Promotion of Science (JSPS)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE
OSTI Identifier:
1425829