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.
During the period from 1998 to 2007, a prospective cohort study of acute myocardial infarction morbidity cases as well as a "case-control" study of arterial hypertension was carried out. The risk of acute myocardial infarction was assessed as well as arterial hypertension; the dose-response relationship and the role of radiation in the mechanism of acute myocardial infarction as well as arterial hypertension development were studied. As a result of this study, a statistically significant increased risk of acute myocardial infarction among the male staff at the Siberian Group of Chemical Enterprises [standardized relative risk = 1.16 (1.04; 1.29)] exposed to external irradiation in comparison with employees unexposed to ionizing radiation was observed. A significant increase in the risk of acute myocardial infarction was observed at external radiation dose accumulation of more than 300 mSv [standardized relative risk = 1.46 (1.09; 1.91)]. The increase in arterial hypertension risk has been established among the analyzed group of employees exposed to long-term irradiation in the absence of the linear dependence of risk, based on cumulative dose of external γ-irradiation [risk due to external radiation dose in the range of 7.3-21.3 mSv = 1.6 (0.96; 2.51) and in the range of external radiation dose 21.4-68.5 mSv = 1.7 (1.04; 2.67) for 68.6-864 mSv = 1.6 (1.01; 2.57)]. This led to the conclusion that radiation can act also as a factor that might potentiate the negative effects of the "traditional" risk factors in the pathogenesis of acute myocardial infarction and hypertension.
It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and Pro were found to have different properties of regulation of TP53-dependent DNA repair target genes, that can effect various levels of chromosome aberrations in cancer patients with these genotypes. Here, we studied frequency of chromatid breaks (CB), chromosome-type aberrations (CTA) and aberrant cells (AC) in cancer patients (n = 102) with various Arg72Pro genotypes. It was shown that the Arg variant of TP53 gene is associated with high frequency of AC and chromatid breaks. That is Arg/Arg carriers have more different chromosome aberrations in comparison to individuals with Arg/Pro and Pro/Pro genotypes (P < 0.05). Conversely, the lowest level of AC and chromatid breaks were detected in cancer patients with the Pro/Pro genotype. A completely unexpected result was that women with Arg/Arg genotype had the most high frequency of CB and AC in comparison to Arg/Pro and Pro/Pro women carriers (P < 0.001). In the group of male patients we did not show any differences in chromosome aberrations between carriers of Arg72Pro genotypes. In conclusion, the TP53 gene Arg72Pro polymorphism appreciably influence on occurrence of chromosome aberrations in cancer.
Investigations aimed at the creation of a standard kit for the synthesis of 99m Tc-labeled ciprofloxacin (fluoroquinolone antibiotic) have been carried out. For isotope labeling, eluate from a technetium-99m generator was added to dry sterile mixtures of ciprofloxacin hydrochloride (CFH) with a reducing agent (tin chloride, SnCl 2 ) in various ratios. The mixtures were incubated for 20 min at room temperature. The influence of components of the reaction mixture on the amount of radiochemical impurity in the resulting radiopharmaceuticals was estimated using TLC. Three 99m Tc-containing complexes and a colloid related to the hydrolysis of tin compounds were formed. The tin content in each complex has been determined by introducing a 117m Sn isotope label. Ways to decrease colloid formation by changing the pH of the medium and by reducing the SnCl 2 concentration in the kit have been investigated. The kit composition has been optimized. It is established that radiopharmaceuticals containing less than 0.175 mg SnCl 2 per 5 mg CFH can be used without additional filtration. Tests on experimental animals (rabbits) with model inflammation in soft tissues showed the functional suitability of 99m Tc-labeled ciprofloxacin for diagnosis of infectious-inflammatory processes.
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