Quantitative assessment of regulatory proteins in blood as markers of radiation effects in the late period after occupational exposure.

The objective of this research was quantitative assessment of serum and membrane regulatory proteins in blood from nuclear workers as markers of radiation-induced alterations in immune homeostasis in the late period after protracted exposure of nuclear workers with different doses. The effector and regulatory lymphocytes were measured using a flow cytofluorometer in workers from the main facilities of the Mayak PA (aged ∼60 y up to 80 y) in the late period after combined exposure to external gamma-rays and internal alpha-radiation from incorporated 239Pu. The control group included non-occupationally exposed members of the Ozyorsk population matched by gender and age to the group of Mayak workers. Thirty serum proteins involved in regulation of immune homeostasis, such as growth factors, multifunctional interleukins, pro- and anti-inflammatory cytokines, and their receptors, were measured using ELISA in blood serum specimens from the Radiobiology Human Tissue Repository. The dosimetry estimates were obtained using Doses-2005. The correlation analysis revealed a statistically significant direct relationship of T-killers and plutonium body burden and a decreasing level of T-helpers with accumulated external dose in exposed individuals. There were differences in expression of membrane markers in young regulatory cells (double null T-lymphocytes, NKT-lymphocytes, regulatory T-cells, and an increase of activated forms of T-lymphocytes), which indicated an active role of regulatory cells in maintaining immune homeostasis in terms of protracted exposure. The assessment of regulatory proteins in blood indicated that growth factors (EGF, TGF-ß1, PDGF), multifunctional interleukins (IL-17A, IL-18), and pro-inflammatory cytokines (IL-1ß and INF-γ) could be potential markers of radiation-induced alterations in protein status. An imbalance of pro- and antiinflammatory proteins in blood and variations of protein profiles at the lower exposure levels (gamma-ray dose <1 Gy, plutonium body burden <0.74 kBq) in the late period after protracted exposure were less pronounced than at the higher exposure levels, which was probably explained by compensatory-adaptive responses in the late period among senile individuals with polypathology.

A repository of bio-specimens from Mayak workers exposed to protracted radiation.

A repository of bio-specimens that includes organs from 700 deceased workers employed at the first nuclear weapons facility "Mayak" and donations of blood, buccal cells, and tissues removed at the time of surgery and/or biopsy from the members of the Mayak cohort undergoing medical treatment or diagnostic procedures has been established at the Southern Ural Biophysics Institute, in Ozyorsk, Russian Federation. The autopsied tissues include formaline-preserved organs, paraffin blocks, and histology slides. For all, occupational, dosimetry, and detailed medical information is available. For 359 individuals, information on malignant tumors, i.e., lung (171), stomach (51), liver (28), and intestine (19), as well as 32 cases of leukemia, are available. External gamma exposures are known for 95% of the 700 autopsies, of whom 560 were exposed to protracted doses exceeding 0.5 Gy, with known maximum annual doses ranging from 0.01-0.5 Gy for about 46%, and annual doses exceeding 0.5 Gy for 48%. Plutonium body burden is known for 73%, of which 40% had body burden greater than 1.5 kBq, and 15% of individuals had body burdens greater than 11.85 kBq. Newly collected specimens include frozen lymphocytes, EBV-immortalized B-cells, frozen erythrocytes, and DNA as well as frozen tumors. Donations were obtained to date from more than 1,600 individuals. For these donors external doses of exposure exceeded 0.5 Gy for 83%, and plutonium body burden exceeded 1.48 kBq for 30%. A Web site describing the Repository that also includes forms for tissue requests can be accessed at http://www.subi.ru/RHTR.