Total gene deletions and mutant frequency of the HPRT gene as indicators of radiation exposure in Chernobyl liquidators

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 a ccident at Chernobyl. HPRT MF was determined using the cloning assay for 11 7 Russian Controls and 122 Liquidators whose blood samples were obtained be tween 1991 and 1998. Only subjects from whom mutants were obtained for dele tion analysis are included. Multiplex PCR analysis was performed on cell ex tracts of 1080 thioguanine resistant clones from Controls and 944 clones fr om Liquidators. Although the deletion spectra of Liquidators and Controls w ere similar overall, the Liquidator deletion spectrum was heterogeneous ove r 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) a nd in 1993-1994 Liquidators (chi(2) = 8.3, p = 0.004), and was marginally e levated relative to 1995-1996 Liquidators (chi(2) = 3.3, p = 0.07). This ty pe of mutation has been highly associated with radiation exposure. Total ge ne deletions were not increased after 1992. Band shift mutations were also increased in the 1991-1992 Liquidators but were associated with increased M F of both Liquidators and Controls (p = 0.009), not with increased MF in 19 91-1992 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 Liqu idators 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 m ore sensitive and persistent indicator of radiation exposure, but the speci ficity of total gene deletions red to detection of probable heterogeneity o f radiation exposure within the exposed population. (C) 1999 Elsevier Scien ce B.V. All rights reserved.