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I{sup 131} therapy induces persistent radiation-dose dependent increases in glycophorin a locus somatic mutations in bone marrow stem cells

Journal Article · · Environmental and Molecular Mutagenesis
OSTI ID:115113
;  [1];  [2];  [3];  [4];  [5]
  1. Univ. of Pittsburgh, PA (United States)
  2. Univ. of California, San Francisco, CA (United States)
  3. Lawrence Livermore National Lab., CA (United States)
  4. National Institutes of Health, Bethesda, MD (United States)
  5. National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD (United States)
Patients with thyroid diseases treated with I{sup 131} receive known sub-acute marrow exposures to ionizing radiation of {approximately}2 to >200 cGy. Time-series sampling of peripheral blood from these patients, assayed for the frequency of erythrocytes expressing glycophorin A (GPA) allele-loss variant phenotypes, demonstrates the induction, accumulation, and long-term persistence of radiation-induced in vivo somatic mutations at this locus in erythroid marrow progenitor cells. Initial dosimetry and assay data from 5 patients yielded a linear GPA dose response of {approximately}6.5 induced variants/10{sup 6} cells/Gy which is 1/3 to 1/4 of that previously observed for Hiroshima A-bomb survivors and individuals exposed at the Chernobyl nuclear reactor and Goiania Cs{sup 137} source accidents who predominantly received external exposures to ionizing radiation. The lower slope of the dose response observed in the I{sup 131} treated patients may reflect a reduced biological effectiveness of this exposure due to differences in the energy spectra of the {gamma} radiation, internal versus external exposure, and/or protracted versus acute dose rate effects. Ongoing studies of I{sup 131} treated patients are designed to define the shape of the low dose response and limit of sensitivity of the GPA assay; parameters that are required for the application of the assay as a quantitative cumulative radiation biodosimeter in medical, occupational, and accidental exposure settings. This biodosimetric analysis of patients receiving very similar marrow exposures will also permit an assessment of the inter-individual variability in biological response to ionizing radiation.
DOE Contract Number:
W-7405-ENG-48
OSTI ID:
115113
Report Number(s):
CONF-9503160--; CNN: Grant 1 RO1 OH03276
Journal Information:
Environmental and Molecular Mutagenesis, Journal Name: Environmental and Molecular Mutagenesis Journal Issue: Suppl.25 Vol. 25; ISSN 0893-6692; ISSN EMMUEG
Country of Publication:
United States
Language:
English

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