This program project will apply a suite of somatic mutation assays to a human population exposed to low-dose, whole-body, ionizing radiation for the dual purpose of defining the exposure and evaluating the dosimetric assays. Approximately 300 Russians exposed to doses in the range of about 5-25 cGy while working to contain and cleanup the Chernobyl accident and 300 controls will be studied over 4 years. The assays are 1) stable chromosome aberrations in lymphocyte detected by fluorescence in situ hybridization; 2) glycophorin A mutation in erythrocytes; and 3) hypoxanthine phosphoribosyltransferase (HPRT) mutation in lymphocytes. Cytogenetics is the classical measure of radiation exposure and is the reference standard. The flow cytometric glycophorin A assay monitors persistent radiation effects in humans, and measures both recombination and deletion events. The proportion of deletion mutations at the HPRT locus will be studied by DNA analysis of mutant cells to determine if it is a more sensitive indicator of persistent radiation damage than HPRT mutant frequency. Preliminary results suggest an exposure effect in each assay, with the effect being clearest in the stable aberrations. Information from each assay will be analyzed independently for: a) its relationship to variables such as age, smoking and diet; b) control mean and variability; c) exposed mean and variability, alone and in relation to control. The combination of responses among assays will be used to estimate: i) the collective mean population dose and its variability; ii) the relative magnitude of response of each assay; iii) the correlation structure among assays, dose, and other variables. The results of this study should determine: the magnitude and nature of the radiobiological injury sustained by the population; the relative merit and optimal deployment of these assays in this and other populations; the utility of these biological dosimeters in the study of low-dose human radiation biology; the advisability of subsequent pursuit of health effects in this population.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Research Program Projects (P01)
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Cancer Centers and Research Programs Review Committee (CCRP)
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Pelroy, Richard
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Lawrence Livermore National Laboratory
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Sigurdson, Alice J; Ha, Mina; Hauptmann, Michael et al. (2008) International study of factors affecting human chromosome translocations. Mutat Res 652:112-21
Noori, Peri; Hou, Saimei; Jones, Irene M et al. (2005) A comparison of somatic mutational spectra in healthy study populations from Russia, Sweden and USA. Carcinogenesis 26:1138-51
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Tucker, James D (2002) Sensitivity, specificity, and persistence of chromosome translocations for radiation biodosimetry. Mil Med 167:8-9
Gardner, Shea N; Tucker, James D (2002) The cellular lethality of radiation-induced chromosome translocations in human lymphocytes. Radiat Res 157:539-52
Thomas, Cynthia B; Nelson, David O; Pleshanov, Pavel et al. (2002) Induction and decline of HPRT mutants and deletions following a low dose radiation exposure at Chernobyl. Mutat Res 499:177-87
Jones, Irene M; Galick, Heather; Kato, Paula et al. (2002) Three somatic genetic biomarkers and covariates in radiation-exposed Russian cleanup workers of the chernobyl nuclear reactor 6-13 years after exposure. Radiat Res 158:424-42
Jones, I M; Tucker, J D; Langlois, R G et al. (2001) Evaluation of three somatic genetic biomarkers as indicators of low dose radiation effects in clean-up workers of the Chernobyl nuclear reactor accident. Radiat Prot Dosimetry 97:61-7

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