PubMed Health⌕ Search

Biomedical subjects

V G Bezlepkin

Publications and source records attributed to V G Bezlepkin.

At least 19 recordsLinked to original sources
PubMed2006

[Changes in copy number and deletion development of mitochondrial DNA in blood cells from breast cancer patients during radiochemotherapy].

Changes in mitochondrial DNA (mtDNA) copy number were compared versus the nuclear beta-globulin gene (internal standard), as well as occurrence of large mtDNA deletions in peripheral blood samples from 21 breast cancer patients following chemoradiotherapy. The study used polymerase chain reaction. Distinct variations were identified both in mtDNA copy number versus nuclear DNA and large mtDNA deletions occurrence in blood cells in response to genotoxic influence of chemoradiotherapy. Some mtDNA copies in breast cancer patients blood cells revealed large deletions whose frequency increased after chemoradiotherapy. Mitochondrial DNA lesions would induce synthesis of mtDNA copies in the course of chemoradiotherapy, which pointed to a compensatory reaction in peripheral blood cells as a consequence of a disturbed energy biogenesis.

Adult↗
PubMed2001

AP-PCR assay of DNA alterations in the progeny of male mice exposed to low-level gamma-radiation.

By comparative analysis of fingerprints of arbitrarily primed polymerase chain reaction (AP-PCR) products, DNA alterations in somatic cells of the progeny (F1 generation) of male mice chronically exposed to low-doses of gamma-radiation was investigated. Male BALB/c mice exposed to 10-50 cGy were mated with unirradiated females 15 days after irradiation. DNA was isolated from biopsies taken from tail tips of 2-month-old progeny. Preliminary AP-PCRs were carried out with 17 primers representing core sequences of micro- and/or minisatellites or their flanking oligonucleotides. Best quantitatively reproduced AP-PCR fingerprints of genomic DNA were obtained with one of these primers, a 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on mouse chromosome 11. Comparative analysis of individual fingerprints of AP-PCR products obtained on DNA templates from the progeny of irradiated and intact males revealed an increased variability of micro-satellite-associated sequences and an increased frequency of "non-parental bands" in DNA-fingerprints from the progeny of males chronically exposed to gamma-radiation 15 days before mating (at the postmeiotic stage of spermatogenesis). The results show that increased micro-satellite instability can be initiated by irradiation of the male parent to subsequently arise or be transmitted to the soma of the F1 generations.

Animals↗
PubMed2000

[Computer analysis of band variability in DNA fingerprints].

Through the example of the distribution of PCR products DNA matrices of mouse tail tissue, a method of comparative analysis of DNA fingerprints is described. The PCR products were obtained using a 20-mer random primer flanking the Atp1b2 locus on mouse chromosome 11. A software program was designed that permits the simplification of comparison of DNA fragments variability or polymorphism detected on electrophoregrams from different individuals.

Animals↗
PubMed1996

The prolongation of survival in mice by dietary antioxidants depends on their age by the start of feeding this diet.

The effect of daily dietary supplements of an antioxidant mixture (AM) consisting of beta carotene, alpha tocopherol, ascorbic acid, rutin, selenium, and zinc on the survival of male C57BL/6 mice starting at 2, 9, 16, and 23 months of age was investigated. The survival of mice given AM starting at 2 and 9 months of age was found to increase significantly (from 86 to 108 days) compared to the control. The times, of 50, 90, and 100% mortality in mice given AM starting at 2 and 9 months of age increased by 16-9.5% compared to the control, whereas in mice given AM, starting at 16 and 23 months of age, no effect was observed.

Aging↗
PubMed1996

Modifying effect in vivo of interferon alpha on induction and repair of lesions of DNA of lymphoid cells of gamma-irradiated mice.

The induction of structural lesions and repair in DNA of lymphoid cells from the peripheral blood, spleen and thymus of mice treated with natural mouse interferon alpha (IFN-alpha) 24 and 48 h prior to gamma irradiation were studied using the comet assay and apurinic-apyrimidinic (AP) site radiolabeling. It was demonstrated that the radiation-induced damage assessed by the comet assay in the DNA of peripheral blood lymphocytes (PBLs), splenocytes and thymocytes of mice treated with IFN-alpha before irradiation was considerably less and was repaired more easily in the postirradiation period than that in untreated mice. The DNA of PBLs and splenocytes from interferon-treated mice showed a decrease in the spontaneously occurring and radiation-induced AP sites, as determined immediately and 90 min after irradiation, compared to the level of AP sites in the DNA of untreated mice. The results lead us to assume that IFN-alpha activates the DNA repair systems in the cells of lymphoid tissue.

Animals↗
PubMed1992

[Mutagenic effect on Escherichia coli bacteria of 8-hydroxy-2'-deoxyguanosine--a DNA base damage product induced by oxygen radicals and ionizing radiation].

The effect of 8-oxo-2'-deoxyguanosine (8-oxo-dG) (8-hydroxydeoxyguanosine)--a DNA base damage product induced by oxygen radicals and irradiation on survival and mutagenesis in Escherichia coli strains C-600 and P-687 was investigated. Survival and mutagenesis curves, in dependence of 8-oxo-dG concentrations in the medium, ranging from 0.2 through 10 mM, were obtained. Bacterial survival at all 8-oxo-dG concentrations tested was shown to be no lesser than in the control. The mutagenic effect of 8-oxo-dG was tested by frequency of reversions in the absence of leucine and threonine. A non-linear dependence of mutagenesis on the concentration was observed. Linear increase in the amount of revertants took place at concentrations of 8-oxo-dG lower than 1 mM, and being kept constant at higher concentrations. Induction of SOS repair under the action of 8-oxo-dG in E. coli PQ37 strain was estimated according to alteration of activity of beta-galactosidase in the SOS chromotest. Weak induction of the SOS response was observed within the wide range of 8-oxo-dG concentration values, which points to a lack of genotoxicity and independence of mutagenesis on SOS repair.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1989

[A decrease in the level of unscheduled DNA synthesis in preparations of irradiated rat hepatocyte nuclei under the effect of polyamines].

The results obtained show the possibility of polyamine (spermine and spermidine) utilization to stabilize the nuclear chromatin and to protect it against nuclease degradation in the course of isolation of liver cell nuclei. Besides, the inhibition of the unscheduled DNA synthesis induced by nuclease incision and by gamma- or UV-radiation was demonstrated in the presence of polyamines.

Animals↗
PubMed1983

Formation of additional contacts of chromosome with membrane in the process of DNA repair synthesis in bacterial cells.

An increase in the amount of membrane-bound DNA was found in B. subtilis cells with UV-induced DNA repair synthesis as compared to untreated cells. It was shown that DNA repair synthesis occurred in DNA membrane complexes (DMC) formed during UV-irradiation. UV-induced formation of DMC was observed in cells of wild type strains which were capable of repairing damaged DNA but not in a mutant defective in DNA-polymerase I. It was demonstrated that DNA-polymerase I is located on the membrane of B. subtilis cells. This suggested a participation of DNA-polymerase I in binding of the chromosome to the membrane in UV-irradiated cells. UV-induced DMC did not dissociate when the cells were treated with inhibitors of DNA-gyrase. It, therefore, was qualitatively different from the DMC found during replication. The mechanisms of binding of the damaged DNA to the membrane in UV-irradiated cells of B. subtilis are discussed.

Bacillus subtilis↗
PubMedDate not supplied

[Study of genome instability using DNA fingerprinting of the offspring of male mice subjected to chronic low dose gamma irradiation].

By a polymerase chain reaction with an arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F1 generation) from male parents of mice exposed to chronic low-level gamma-radiation was studied. Male BALB/c mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old offspring mice and DNA was isolated. The primer in the AP-PCR was a 20-mer oligonucleotide flanking the microsatellite locus Atp1b2 on chromosome 11 of the mouse. A comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of microsatellite-associated sequences in the genome of the offspring of the males exposed to 25 and 50 cGy. The DNA-fingerprints of the offspring of male mice exposed to chronic irradiation with the doses 10 and 25 cGy 15 days before fertilization (at the post-meiotic stage of spermatogenesis) showed an increased frequency of "non-parent bands". The results of the study point to the possibility of transmission to the offspring somatic cells of changes increasing genome instability from male parents exposed to chronic low-level radiation prior to fertilization.

Animals↗
PubMedDate not supplied

[Micronucleus frequency is increased in bone marrow erythrocytes from offspring of male mice exposed to chronic low-dose gamma irradiation].

The micronucleus frequency in bone marrow erythrocytes from the F1 progeny of male mice exposed to chronic low-dose gamma-irradiation was determined. Male BALB/c mice were irradiated with 10, 25 and 50 cGy at dose rates of 1, 5, and 15 cGy/day and mated with unirradiated females on day 15 after irradiation. The obtained offspring had an elevated micronucleus frequency in bone marrow erythrocytes at the age of 2 months. This suggests the transmission of genome instability from damaged germ-line cells of irradiated male parents to somatic cells of the progeny.

Animals↗
PubMedDate not supplied

[Induced germ line genomic instability at mini- and micro-satellites in animals].

The recent data on the phenomenon of the induced germline genomic instability at mini- and microsatellites in animals were considered. Natural hypervariability of the minisatellites and microsatellites and their abundance in eukaryotic genome provide it's utility as the useful genetic markers for evaluation of the germline mutation frequency induced by treatment with different type of genotoxic factors at the low doses. High sensitivity of assays and possibility for direct determinations of the mutations, without the necessity to use extrapolation, are ensured. Some discussion is presented on the role of non-targeted mechanisms for the radiation-prone DNA lesions in the induction of germline genomic instability and also on the involving in this process the recombination events upon meiosis or during the early development stages of embryos. It is proposed that quantitative determination of germline genomic instability rate may be used as an acceptable variant for the genetic risk assessment and as indicator of increased probability for cancer and other pathologies at the offspring born to irradiated parents.

Adult↗
PubMedDate not supplied

[The increase in the variability of microsatellite-associated repeats in the genome of gamma-irradiated male mice is tissue specific].

The arbitrarily primed polymerase chain reaction (AP-PCR) was used to measure the level of polymorphism of microsatellite (MCS)-associated repeating sequences of spleen, lung, and brain DNA in the F1 progeny of male BALB/c mice exposed to acute gamma-radiation at doses of 50 cGy and 200 cGy 15 days before mating with unirradiated females. The variability of MCS-associated sequences in the genome of brain and lung cells was higher as compared to the spleen cells of the progeny of unirradiated males. In the progeny of irradiated males, a 20% increase in MCS polymorphism of spleen DNA was found as an increase in the frequency of "non-parent" bands in DNA-fingerprints as against to the progeny of unirradiated males. Significant changes in this parameter were revealed for brain tissue and not for lung tissue only in the progeny of males exposed to 200 cGy. The results suggest a tissue-specific character of transmission of radiation-induced alterations in the genome of germ cells of male parents to the somatic cells of the progeny.

Animals↗
PubMedDate not supplied

[Increase of mitochondrial DNA copies with low level of DNA repair in tissue cells of gamma-irradiated mice].

The damage and the change in the number of mitochondrial DNA (mtDNA) copies in brain and spleen tissues of gamma-irradiated mice were studied. The changes in the number of mitochondrial DNA (mtDNA) copies were assayed by the comparative analysis of the density values of long-extension PCR products of the mtDNA fragments (16 kb) and the cluster nuclear gene of beta-globin (8.7 kb). PCRs of mtDNA fragments and the nuclear gene of beta-globin were carried out simultaneously in one test-tube within total DNA. Our results showed that in brain and in spleen cells of mice exposed to gamma-radiation an increase in copy number (polyploidization) of mtDNA with regard to the nuclear gene beta-globin took place. The induction of polyploidization of mtDNA observed in cells of gamma-irradiated animals is regarded as the development of a compensatory reaction because of the energy deficiency due to the increased ATP consumption and structural alteration of genes controlling OXPHOS. The data enabled the assumption that because of the low efficiency of repair systems in mitochondria the induction of synthesis of new mtDNA copies on intact or little affected mtDNA templates may be the major mechanism for the retention of the mitochondrial genome which is constantly damaged by the endogenous ROS and is affected by ionizing radiation and/or other exogenous factors.

Animals↗