Different patterns of allelic imbalance in sporadic tumors and tumors associated with long-term exposure to gamma-radiation.

The study aimed to reveal cancer related mutations in DNA repair and cell cycle genes associated with chronic occupational exposure to gamma-radiation in personnel of the Siberian Group of Chemical Enterprises (SGCE). Mutations were analyzed by comparing genotypes of malignant tumors and matched normal tissues of 255 cancer patients including 98 exposed to external gamma-radiation (mean dose 128.1±150.5mSv). Also a genetic association analysis was carried out in a sample of 149 cancer patients and 908 healthy controls occupationally exposed to gamma-radiation (153.2±204.6mSv and 150.5±211.2mSv, respectively). Eight SNPs of genes of DNA excision repair were genotyped (rs13181, rs1052133, rs1042522, rs2305427, rs4244285, rs1045642, rs1805419 and rs1801133). The mutation profiles in heterozygous loci for selected SNP were different between sporadic tumors and tumors in patients exposed to radiation. In sporadic tumors, heterozygous genotype Arg/Pro of the rs1042522 SNP mutated into Arg/0 in 15 cases (9.6%) and 0/Pro in 14 cases (8.9%). The genotype Lys/Gln of the rs13181 SNP mutated into Lys/0 and 0/Gln in 9 and 4 cases, respectively. In tumors of patients exposed to low-level radiation, the rs1042522 Arg/0 mutated genotype was found in 12 cases (12.1%), while in 2 cases (2%) 0/Pro mutation was observed. Finally, the rs13181 0/Gln mutated genotype was observed in 15 cases (16,5%) . Thus, our study showed the difference in patterns of allelic imbalance in tumors appeared under low-level radiation exposure and spontaneous tumors for selected SNPs. This suggests different mechanisms of inactivation of heterozygous genotypes in sporadic and radiation-induced tumors.

The bank of biological samples representing individuals exposed to long-term ionizing radiation at various doses.

Collection and storage of biological specimens in biobanks aims to obtain and preserve samples of different kinds for biological and medical studies. Here we present a description of the Bank of Biological Materials (BBM) housed by the Seversk Biophysical Research Centre (SBRC; Seversk, Russia). The main goal of maintaining the BBM is to collect and store biological samples suitable for genetic studies of people exposed to long-term ionizing radiation. Currently, the collection includes 19,194 biological specimens obtained from 8105 donors, of whom 42.3% are diagnosed with malignant neoplasms, 28.7% are healthy residents of the city of Seversk, 18.8% are healthy employees of the Siberian Group of Chemical Enterprises (SGCE), and 10.2% are patients diagnosed with acute myocardial infarction. The donors were enrolled using the Regional Medical and Dosimetric Register database created by the SBRC. For each donor, DNA specimens were extracted from peripheral blood and tissues and cell suspensions for cytogenetic analysis were prepared routinely. The BBM's unique collection is suitable primarily for studies of individual radiosensitivity of humans (IRH), and genetic aspects of the pathophysiology of common human diseases, especially in populations exposed to long-term low-dose ionizing radiation.