Long-term cellular effects in humans chronically exposed to ionizing radiation.

The aim of the study was to investigate hematopoietic injury and recovery in residents of the Techa riverside villages who had been chronically exposed to radiation as a result of the activities of the Mayak Nuclear Facility, and evaluate late effects from chronic, low-dose radiation exposures. Whole blood samples were drawn from 338 unexposed individuals resident in noncontaminated villages, and 692 individuals chronically exposed externally (to primarily gamma radiation) and internally from Sr since 1949 at decreasing dose-rates which have currently reached the background levels. The mean cumulative dose in the exposed cohort was 0.62 Gy over the years 1949 to 2008 using the Techa River Dosimetry System (TRDS) 2000. The frequency of chromosome aberrations and mutations in peripheral lymphocytes, and other aspects indicative of cellular and molecular repair of radiation damage, were measured. The subjects were divided into two study groups: (a) 171 individuals who during the early exposure period (where the highest dose-rates were prevalent) were noted to manifest leucopenia and/or were diagnosed with chronic radiation syndrome (CRS), and (b) 521 exposed individuals without cytopenia and CRS. The first group demonstrated an increased frequency of micronuclei, dicentric chromosomes, somatic mutations (CD3-CD4+cells) in lymphocytes, and mutations in the TP53 gene. In addition, they demonstrated a lower Cu/Zn-SOD concentration, a significantly increased concentration of nitric oxide, and a greater apoptotic frequency in peripheral blood lymphocytes compared to exposed individuals without leucopenia. Similar to the unexposed individuals, the second group demonstrated "background levels" of mutational frequencies several years after their exposures, but they did show an increased number of cells with delayed cell cycles based on Chk-2 concentrations compared to the unexposed population. The data are consistent with the idea that a chronic radiation exposure within a dose range from 0.01 Gy to 1.96 Gy results in more severe late hematopoietic effects in a select cohort of highly radiosensitive individuals, rather than an overall increase in late effects in cells of each exposed individual. The authors state that radiation-exposed subjects demonstrating CRS showed an activation of barrier anti-oxidative stress mechanisms at late periods after radiation exposure, apparently in response to a more severe radiation damage than subjects exposed to similar radiation doses but not demonstrating CRS. Finally, the persistence of chromosome aberrations and somatic mutations in the CRS cohort is indicative of an exhaustion of the anti-oxidative stress mechanisms responding for so many years after the exposure, leading to genomic instability.