title: Total gene deletions and mutant frequency of the HPRT gene as indicators of radiation exposure in Chernobyl liquidators.
abstract: This study was conducted to determine the utility of deletion spectrum and mutant frequency (MF) of the hypoxanthine phosphoribosyl transferase gene (HPRT) as indicators of radiation exposure in Russian Liquidators who served in 1986 or 1987 in the clean up effort following the nuclear power plant accident at Chernobyl. HPRT MF was determined using the cloning assay for 117 Russian Controls and 122 Liquidators whose blood samples were obtained between 1991 and 1998. Only subjects from whom mutants were obtained for deletion analysis are included. Multiplex PCR analysis was performed on cell extracts of 1080 thioguanine resistant clones from Controls and 944 clones from Liquidators. Although the deletion spectra of Liquidators and Controls were similar overall, the Liquidator deletion spectrum was heterogeneous over time. Most notable, the proportion of total gene deletions was higher in 1991-1992 Liquidators than in Russian Controls (chi 2 = 10.5, p = 0.001) and in 1993-1994 Liquidators (chi 2 = 8.3, p = 0.004), and was marginally elevated relative to 1995-1996 Liquidators (chi 2 = 3.3, p = 0.07). This type of mutations has been highly associated with radiation exposure. Total gene deletions were not increased after 1992. Band shift mutations were also increased in the 1991-1992 Liquidators but were associated with increased MF of both Liquidators and Controls (p = 0.009), not with increased MF in 1991-1992 Liquidators (p = 0.7), and hence are not believed to be associated with radiation exposure. Regression analysis demonstrated that relative to Russian Controls HPRT MF was elevated in Liquidators overall when adjusted for age and smoking status (37%, p = 0.0001), and also was elevated in Liquidators sampled in 1991-1992 (72%, p = 0.0076), 1993-1994 (22%, p = 0.037), and 1995-1996 (62%, p = 0.0001). In summary, HPRT MF was found to be the more sensitive and persistent indicator of radiation exposure, but the specificity of total gene deletions led to detection of probable heterogeneity of radiation exposure within the exposed population.
authors.affiliation: Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, CA 94550, USA. jones20@llnl.gov
authors.forename: I M
authors.initials: IM
authors.lastname: Jones
authors.forename: C B
authors.initials: CB
authors.lastname: Thomas
authors.forename: K
authors.initials: K
authors.lastname: Haag
authors.forename: P
authors.initials: P
authors.lastname: Pleshanov
authors.forename: I
authors.initials: I
authors.lastname: Vorobstova
authors.forename: L
authors.initials: L
authors.lastname: Tureva
authors.forename: D O
authors.initials: DO
authors.lastname: Nelson
mesh_terms: D000328:Adult; D017353:Gene Deletion; D005787:Gene Frequency; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000528:radiation effects*; D008875:Middle Aged; D009154:Mutation; D016273:Occupational Exposure; D011210:Power Plants; D018788:Radioactive Hazard Release; D012044:Regression Analysis; D012426:Russia; D012907:Smoking
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase