This project seeks to utilize state-of-the-art molecular cytogenetic techniques to determine the frequency and persistence of stable cytogenetic damage in peripheral T lymphocytes of victims of the Chernobyl nuclear reactor accident. the subjects involved in this study fall into two groups: those who received high whole-body doses (ranging from ~0.8 to ~6 Gy), and those who were exposed more slowly (over a period of one or a few days) and received ~0.25 Gy. Fluorescence in situ hybridization of chromosome-specific composite DNA probes (""""""""chromosome painting"""""""") will be used to measure the frequency of stable chromosome aberrations, i.e. translocations. These results will be validated against the conventional method of G-banding. In a cross-sectional component of this study, 60 people whose exposures range from 0 (matched controls) to the highest surviving doses will be examined. Accurate exposure estimates will be made and used as a benchmark against which the results of the glycophorin A, HPRT, and germinal mutation portions of this Program Project will be compared. The dosimetry will also be used to guide the selection of subjects for a longitudinal component of this study. Here, 16 subjects who span the dose range will be examined for five consecutive years. The proposed work will lead to a greatly improved understanding of the temporal stability of various cytogenetic anomalies (particularly translocations), the extent of clonal expansion following radiation exposure, the effects of dose on translocation stability nd clonal expansion, and the utility of chromosome painting as a reliable and effective biodosimeter following accidental radiation exposure. In conjunction with the GPA, HPRT, and germinal mutation efforts of this Program Project, this work will lead to a greatly increased understanding of the long-term effects of human exposure to ionizing radiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA059431-04
Application #
3731572
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
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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
Jones, I M; Thomas, C B; Xi, T et al. (2005) The genetic basis for variation in radiation sensitivity in the general population. Radiat Res 163:700-1
Tucker, James D; Cofield, Jackie; Matsumoto, Kyomu et al. (2005) Persistence of chromosome aberrations following acute radiation: I, PAINT translocations, dicentrics, rings, fragments, and insertions. Environ Mol Mutagen 45:229-48
Tucker, James D; Cofield, Jackie; Matsumoto, Kyomu et al. (2005) Persistence of chromosome aberrations following acute radiation: II, does it matter how translocations are scored? Environ Mol Mutagen 45:249-57
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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