Papers by Alexander Rubanovich
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
Annually during six years since 1986 dynamics of the mutation load in Arabidopsis populations was... more Annually during six years since 1986 dynamics of the mutation load in Arabidopsis populations was studied. Frequency of the embryonic lethal mutations was studied with Muller embryonic test. First two years after the accident an increase of mutation load in Arabidopsis populations was observed at all levels of radioactive contamination. In the areas with contamination up to 10 mR/h the mutation load decreased to the control level by 1990. In the areas with contamination up to 130 mR/h the mutation load exceeds the control by 4-8 times.
Thyroid, 2017
Background: Several functional SNPs at the FOXE1 locus on chromosome 9q22.33 have been associated... more Background: Several functional SNPs at the FOXE1 locus on chromosome 9q22.33 have been associated with the risk for papillary thyroid carcinoma (PTC). This study set out to elucidate whether their effects are independent, using genotyping results in populations of Asian and European descent. Methods: Single-nucleotide polymorphisms (SNPs) rs965513 and rs1867277, and a polymorphic region determining the length of FOXE1 polyalanine (poly-Ala) tract were genotyped in 501 patients with PTC and 748 healthy individuals from Japan, and in 660 patients and 820 population controls from Belarus. Functional analysis of transactivation activities of FOXE1 isoforms with varying number of alanine repeats was performed by a dual luciferase assay. Results: All three polymorphisms were significantly associated with PTC in both populations on univariate analysis. However, conditional analysis revealed independent effects of rs965513 and rs1867277 SNPs, but not of the FOXE1 poly-Ala polymorphism. The independent effect of the lead rs965513 SNP was observed in both populations, while that of rs1867277 was only identified in the Japanese population, in which linkage disequilibrium between the three polymorphisms is markedly weaker. Despite the strong decrease in transcriptional activity with increasing FOXE1 poly-Ala tract length, no difference in transactivation potential of the FOXE1 poly-Ala isoforms could be seen after adjustment for the minimal promoter activity in the reporter vectors. Plasmids encoding FOXE1 isoforms of increasing poly-Ala tract length were also found to produce less FOXE1 protein after cell transfection. Conclusions: The functional variants, rs965513 and rs1867277, independently contribute to genetic predisposition to PTC, while a contributing role of the FOXE1 poly-Ala polymorphism could not be confirmed.
Environmental Pollution, 2018
Hypermethylation of СpG islands in the promoter regions of several genes with basic protective fu... more Hypermethylation of СpG islands in the promoter regions of several genes with basic protective function in blood leukocytes of individuals exposed to ionizing radiation long time ago (2e46 years), and differential effects of age and radiation exposure on hypermethylation was reported in our previous work. To validate these results, epigenetic modifications were assessed in an independent series of 49 nuclear industry workers from the "Mayak" facility (67e84 years old at sampling) with documented individual accumulated doses from the prolonged external g-radiation exposure (95.9e409.5 cGy, end of work with radiation:0.3e39 years ago), and in 50 non-exposed persons matched by age. In addition to the genes analyzed before (RASSF1A, p16/INK4A, p14/ARF, GSTP1), four additional loci were analyzed: TP53, ATM, SOD3, ESR1. The frequency of individuals displaying promoter methylation of at least one of the 8 genes (71.4%) was significantly higher in exposed group as compared to the control group (40%), p ¼ .002, OR ¼ 3.75. A significantly elevated frequency of individuals with hypermethylated СpG islands in GSTP1, TP53, SOD3 promoters was revealed among exposed subjects as compared to the control group (p ¼ .012, OR ¼ 8.41; p ¼ .041, OR ¼ 4.02 and p ¼ .009, OR ¼ 3.42, respectively). A similar trend (p ¼ .12, OR ¼ 3.06) was observed for the p16/INK4A gene. As a whole, p16/INK4A and GSTP1 promoter hypermethylation in irradiated subjects from both previously and currently analyzed groups was pronounced. Thus, the direction of the effects was fully confirmed, suggesting the result reproducibility. No statistically significant correlation between promoter methylation and individual radiation dose was found. Further studies are required to create an array of blood epigenetic markers of radiation exposure associating with premature aging and age-related diseases and to accurately evaluate radiation-added effect across the range of doses. Synthesis: The results of studies of epigenetic changes in two independent samples of irradiated subjects indicated the significance of radiation factor in the induction of hypermethylation of CpG islands in gene promoters that is revealed in blood cells years and decades after exposure.
PLoS ONE, 2012
The non-targeted effects of human exposure to ionising radiation, including transgenerational ins... more The non-targeted effects of human exposure to ionising radiation, including transgenerational instability manifesting in the children of irradiated parents, remains poorly understood. Employing a mouse model, we have analysed whether low-dose acute or low-dose-rate chronic paternal c-irradiation can destabilise the genomes of their first-generation offspring. Using single-molecule PCR, the frequency of mutation at the mouse expanded simple tandem repeat (ESTR) locus Ms6-hm was established in DNA samples extracted from sperm of directly exposed BALB/c male mice, as well as from sperm and the brain of their first-generation offspring. For acute c-irradiation from 10-100 cGy a linear dose-response for ESTR mutation induction was found in the germ line of directly exposed mice, with a doubling dose of 57 cGy. The mutagenicity of acute exposure to 100 cGy was more pronounced than that for chronic low-dose-rate irradiation. The analysis of transgenerational effects of paternal irradiation revealed that ESTR mutation frequencies were equally elevated in the germ line (sperm) and brain of the offspring of fathers exposed to 50 and 100 cGy of acute c-rays. In contrast, neither paternal acute irradiation at lower doses (10-25 cGy), nor low-dose-rate exposure to 100 cGy affected stability of their offspring. Our data imply that the manifestation of transgenerational instability is triggered by a threshold dose of acute paternal irradiation. The results of our study also suggest that most doses of human exposure to ionising radiation, including radiotherapy regimens, may be unlikely to result in transgenerational instability in the offspring children of irradiated fathers.
Ecological genetics, Jun 15, 2010
ВСТРЕЧАЕМОСТЬ TCR-МУТАНТНЫХ ЛИМФОЦИТОВ У ЧЕЛОВЕКА В ЗАВИСИМОСТИ ОТ ГЕНОТИПОВ ПО ЛОКУСАМ ДЕТОКСИКА... more ВСТРЕЧАЕМОСТЬ TCR-МУТАНТНЫХ ЛИМФОЦИТОВ У ЧЕЛОВЕКА В ЗАВИСИМОСТИ ОТ ГЕНОТИПОВ ПО ЛОКУСАМ ДЕТОКСИКАЦИИ КСЕНОБИОТИКОВ л. е. сальникова © 1 , и. а. Замулаева 2 , о. б. белопольская 1 , т. и. иванова 2 , г. и. кузнецова 1 , а. с. саенко 2 , с. к. абилев 1 , а. в. рубанович 1
Environmental Research, 2016
Ecological genetics
The composition of 5 populations of Adalia bipunctata L. of the Norway and two populations of the... more The composition of 5 populations of Adalia bipunctata L. of the Norway and two populations of the Kola Peninsula was stu died. The proportion of black color imago in them varies from 0% to 35.7%. The composition of the populations of A. bipunctata inhabiting the Arctic Circle is described for the first time. Standard correlation analysis did not reveal a significant dependence of the proportion of black individuals, both on the latitude of habitats, and on their climatic parameters. Application of the logistic regression method to these data made it possible to show that the abundance of black morphs is positively associated with the average winter temperature, and is negatively correlated with summer moisture and mean temperature. Basically, these data are determined by the peculiarities of the Bergen population, where the greatest concentration of melanists is observed, and the climatic conditions (according to the average winter temperature, humidity and annual amount of atmosphe...
Introduction Long-term studies in the field of radiation cytogenetics have resulted in the discov... more Introduction Long-term studies in the field of radiation cytogenetics have resulted in the discovery of relationship between induction of chromosome aberrations and the type of ionizing radiation, their intensity and dose. This has served as a basis of biological dosimetry as an area of application of the revealed relationship, and has been used in the practice to estimate absorbed doses in people exposed to emergency irradiation [1,2]. The necessity of using the methods of biological dosimetry became most pressing in connection with the Chernobyl accident in 1986, as well as in connection with other radiation situations that occurred in nuclear industry of the former USSR. The materials presented in our works [3-8] demonstrate the possibility of applying cytogenetic methods for assessing absorbed doses in populations of different regions exposed to radiation as a result of accidents at nuclear facilities (Chernobyl, the village Muslyumovo on the Techa river, the Three Mile Island n...
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Gigiena i sanitariia
The genotypic associations of the frequencies of spontaneous and radiation-induced chromosome abe... more The genotypic associations of the frequencies of spontaneous and radiation-induced chromosome aberrations in human lymphocytes were studied to develop genetic tests for elevated and reduced radiosensitivity. Cytogenetic analysis and genotyping (19 sites of detoxification and DNA repair genes) were carried out for a sample of Chernobyl cleanup workers (n = 83) and for a homogenous control sample of volunteers (n = 99). In both groups, the frequency of chromosome-type aberrations proved to be elevated in carriers of minor alleles in the XPD gene (sites T2251G (Lys751Gln) and G862A (Asp312Asn)) and a combination of GSTM1-GSTT1-positive genotypes. The polymorphism of these gene did not affect the frequency of gamma-radiation-induced aberrations in the controls (1 Gy in vitro), which was associated with the alleles of the OGG1, XRCC1, and CYP1A1 genes. Thus, the frequencies of spontaneous and in vitro induced chromosome-type aberrations are associated with the alleles of different xenobi...
Gigiena i sanitariia
A study to evaluate congenital morphogenetic variants (CMGVs) and the association of the polymorp... more A study to evaluate congenital morphogenetic variants (CMGVs) and the association of the polymorphism of the xenobiotic detoxification and repair genes with cytogenetic parameters was conducted for the first time in children living in different climatic zones and areas polluted with primary petroleum refining products. Analysis of CMGVs and cytogenetic parameters in children points to the total genotoxic impact of oil pollutions. The children's higher sensitivity to environmental pollution is associated with the polymorphism of the detoxification gene, with the base excision repair gene XRCC1 in particular.
Alcohol abuse is one of the main reasons behind the low life span in Russia. Both social and gene... more Alcohol abuse is one of the main reasons behind the low life span in Russia. Both social and genetic factors affect the alcohol consumption level. The genetic factors are alleles of the alcohol dehydrogenase ADH1B and aldehyde dehydrogenaseALDH2 genes. We have typed and found frequencies for the alleles in a cohort of 642 men, ethnic Russians. The individuals of the cohort were asked to complete a questionnaire in the framework of the Izhevsk Family Study (Leon et al., 2007, 2009) regarding the amount of alcohol consumed and on the type of hazardous alcohol consumption (nonbeverage alcohol consumption and the so-called "zapoï" which is a Russian term for a heavy drinking bout lasting for at least 2 days, when an individual is withdrawn from the normal social life). The ADH1B*48His allele was found among heterozygous individuals only (N=68, 10.6% of the cohort). The ALDH2*504Lys allele was also found among heterozygous individuals only (N=2, 0.3%) The effect of ADH1B allele...
NATO Science for Peace and Security Series C: Environmental Security, 2011
ABSTRACT The data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood... more ABSTRACT The data on the frequencies of chromosome aberrations in lymphocytes of peripheral blood of 99 volunteers depending on genotypes by genes of xenobiotics detoxification before and after γ-irradiation with the dose of 1 Gy in vitro are presented. The frequencies of aberrations were estimated by analyzing not less than 500–1,000 metaphases per person. The data of the cytogenetic analysis were compared with the results of PCR genotyping by the genes of xenobiotics detoxication (CYP1A1, CYP2D6, GSTM1, GSTT1, GSTP1, COMT, NAT2), genes of DNA repair (XRCC1, XPD, ERCC1, APEX1, RAD23B, OGG1, ATM) as well as by the genes of oxidative response and cell cycle regulation (SOD2, CAT, GCLC, MTHFR, Tp53). The frequency of spontaneous aberrations of chromosome type was reduced for homozygotes by the deletion of GSTM1 locus, especially for double homozygotes by the deletions of GSTM-GSTT1 genes. The mentioned frequency increased additively with the number of copies of the minor allele variants XPD*2251 G and XPD*862A of gene of excision repair XPD (p = 0.025). The frequency of γ-induced chromosome aberrations proved to be elevated for the carriers of a minor allele OGG1*977 G (p = 0.011). The significantly elevated number of γ-induced chromosome aberrations was also observed for the carriers of major alleles XRCC1*G1996 and XRCC1*C580 (p = 0.002). The frequency of γ-induced chromosome aberrations proved to be reduced for G/G homozygotes by a minor allele of poorly studied site CYPA1T606G: 0.094 ± 0.006 against 0.112 ± 0.002 for the carriers of allele T (p = 0.004). The results of meta-analysis of the data of 14 works on the effect of genotype by GSTM1 locus on the frequency of cytogenetic anomalies in the control and exposed populations are discussed. KeywordsGenetic polymorphism-DNA repair genes-Associative studies-Chromosome radiosensitivity-Gamma radiation in vitro-Chromosome aberrations
Central European Journal of Biology, 2014
ABSTRACT Background: Accumulation of evidence about the epigenetic regulation of genome function ... more ABSTRACT Background: Accumulation of evidence about the epigenetic regulation of genome function suggests the necessity to explore new aspects of the genotoxic action of radiation on the human body. Methodology: A methylation-sensitive PCR assay was used to analyze promoter methylation of p16/CDKN2A, p14/ARF, RASSF1A and GSTP1 genes in blood leukocytes from 103 unirradiated volunteers and 104 irradiated subjects (83 Chernobyl Nuclear Power Plant liquidators and 21 nuclear specialists). Additionally, 21 families whose fathers were nuclear specialists were examined. Results: A significantly elevated frequency of individuals with abnormal methylation of p16/CDKN2A and GSTP1 genes was revealed in the exposed group compared to the control group (p = 0.0097 and p = 0.005, respectively). The occurrence of promoter methylation of RASSF1A gene significantly correlated with aging both in the control group (r = 0, 213; p = 0.006) and in the exposed individuals (r = 0, 212; p = 0,031). No methylated genes were found in the offspring of control families. Conclusion: Our study showed for the fist time that prolonged radiation exposure at low and medium doses is associated with hypermethylation of genes involved in the basic protective functions of cells; an effect that is persistent in blood leukocytes for significant periods after irradiation.
General Reanimatology, 2011
Acta naturae, 2010
This study presents the results of research on DNA polymorphism in children with malignant brain ... more This study presents the results of research on DNA polymorphism in children with malignant brain tumors (172 patients, 183 in the control group). Genotyping was performed using an allele-specific tetraprimer reaction for the genes of the first (CYP1A1 (2 sites)) and second phases of xenobiotic detoxication (GSTM1, GSTT1, GSTP1, GSTM3), DNA repair genesXRCC1, XPD(2 sites),OGG1, as well asNOS1andMTHFR.The increased risk of disease is associated with a minor variant ofCYP1A1(606G) (p = 0.009; OR = 1.50) and a deletion variant ofGSTT1, (p = 0.013, OR = 1.96). Maximum disease risk was observed in carriers of double deletions inGSTT1-GSTM1(p = 0.017, OR = 2.42). The obtained results are discussed in reference to literary data on the risk of malignant brain tumor formation in children and adults.
Gene, Jan 17, 2015
Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene... more Single nucleotide polymorphisms (SNPs) of the secretory phospholipase A2 type IIa (sPLA-IIa) gene (PLA2G2A) affect sPLA2-IIa level and activity in patients with diabetes mellitus, acute coronary syndrome or recent cardiovascular surgical interventions. Our study examined the effects of PLA2G2A SNPs on sPLA2-IIa levels and activity in patients with stable CHD. The study included a total of 396 patients (30% women). Six SNPs of PLA2G2A: rs1774131, rs11573156, rs3753827, rs2236771, rs876018, and rs3767221, sPLA2-IIa level and activity were determined for all patients. Four SNPs (rs1774131, rs11573156, rs3753827, rs3767221) correlated with sPLA2-IIa level but not activity with the strongest correlation observed for rs11573156 (r=0.49, p=3.7·10(-13)). All partial correlations controlling for rs11573156 became insignificant, whereas, the partial correlation of rs11573156 with sPLA2-IIa level controlling for other SNPs remained significant. Only rs11573156 showed association with sPLA2-IIa...
Vestnik Rossiĭskoĭ akademii meditsinskikh nauk / Rossiĭskaia akademiia meditsinskikh nauk, 2011
The study included 243 patients with acute community-acquired pneumonia and 173 healthy subjects.... more The study included 243 patients with acute community-acquired pneumonia and 173 healthy subjects. The following candidate loci were used to investigate genetic variability: 3 sites of CYP1A1, GSTM1, GSTT1, GSTP1, ACE gene of the rennin-angiotensin system, chemokine receptor gene CCR5. Enhanced predisposition to pneumonia was shown to be characteristic of homozygotes in deletion at the ACE locus (OR = 1.8; p = 0.013), carriers of normal alleles of the GSTM1 locus (OR = 1.7; p = 0.010), and homozygotes in allele 606T of the CYP1A1 gene (OR = 1.6; p = 0.020).
Radiatsionnaia biologiia, radioecologiia / Rossiĭskaia akademiia nauk
Annually during six years since 1986 dynamics of the mutation load in Arabidopsis populations was... more Annually during six years since 1986 dynamics of the mutation load in Arabidopsis populations was studied. Frequency of the embryonic lethal mutations was studied with Muller embryonic test. First two years after the accident an increase of mutation load in Arabidopsis populations was observed at all levels of radioactive contamination. In the areas with contamination up to 10 mR/h the mutation load decreased to the control level by 1990. In the areas with contamination up to 130 mR/h the mutation load exceeds the control by 4-8 times.
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Papers by Alexander Rubanovich