Genetic risk assessment for workers in nuclear power plants using chromosomal aberrations and copy number variation

Abstract

Nowadays, due to the strict radiation protection/safety program, current levels of exposure to ionizing radiation (IR) in occupation have decreased and are far below the regulatory limit established by the International Commission on Radiological Protection (ICRP), however personal cumulative doses in nuclear power plant workers are continuously increasing. The biological and genetic effects of low-dose level of IR exposure and its relationship to carcinogenesis have received great attention in the last years. The aim of the present study is to assess occupationally induced chromosomal damage in relation to copy number variation in a large population of nuclear power plant workers exposed to chronic low dose IR. For this purpose, we used the Chromosome aberration (CA) and micronuclei (MN) assay in peripheral blood lymphocytes (PBL) of nuclear power plant workers never exceeded 20 mSv per year for their duration of work and compare the results with control individuals. And furthermore we investigated for the first time the influence of Glutathione S-Transferase mu 1 (GSTM1) and theta 1 (GSTT1) copy number variations (CNVs) on chromosomal damage in low dose IR-exposed workers. In this study, the CA frequency was significantly higher in radiation exposed workers than controls (Mann-Whitney test, p < 0.001), and chromosome-type aberration frequency was significantly increase with the recent 1.5-year dose (Pearson's correlation coefficient test

r = 0.17, p = 0.02). The Poisson regression analyses revealed that chromosome-type aberration was significantly associated with recent 1.5-yr dose after adjusting for confounding variables such as age, smoking and alcohol intake. when exposure workers were divided into two groups based on the median split (high and low exposure groups), in relatively high exposure group, we found a negative correlation between the frequencies of Chromatid-type aberration and GSTM1 and GSTT1 copy number (Kendall's Tau = -0.17, p = 0.058 and Kendall's Tau = -0.17, p = 0.054, respectively),and the frequency of Chromatid-type aberration increased as the each copy number of GSTM1 and GSTT1 deletion variants increased from zero to one to two after adjusting for confounding variables such as age, smoking and alcohol intake. In addition, a significant negative association between combined copy number of GSTM1/GSTT1 and chromatid-type aberrations have shown in relatively high exposed group after considering confounding variables (Frequency ratio = 0.84, 95% CI 1.23 - 4.39, p = 0.009) and gene-environment interaction between radiation exposure and the sum of GSTM1 and GSTT1 gene copy number in occurrence of chromatid type aberratoins have also been observed In conclusion, our current results reconfirm the usefulness of chromosome aberrations assay as a early effective markers for individual monitoring and diagnosis of occupationally exposed to low levels of IR. A clear inverse association between copy number of GSTM1 and GSTT1 and the frequency of chromosomal aberrations in radiation workers present putative markers of individual susceptibility to IR-induced DNA damage.