General conclusion on the Laboratory of Radiation Biology poster session Programme Advisory Committee for Condensed Matter Physics 32 nd meeting, June 2010 Oleg V. Belov (Laboratory of Radiation Biology, JINR Dubna)

1. Study of the regularities in the induction of different types of DNA lesions, apoptosis, and repair in human lymphocytes in different phases of the cell cycle under ionizing radiation with different physical properties in the presence of modifiers

Induction and Repair of DNA Double-Strand Breaks in Human Lymphocytes after Irradiation by γ-Rays and Boron Ions V.N. Chausov, E.V. Baranova, A.V. Boreyko, E.V. Ilyina, I.I. Ravnachka, S.I. Tiunchik 1. Regularities of the formation of DNA double strand breaks and the kinetics of their repair in the presence of the mentioned modifiers under irradiation with γ-rays and boron ions have been studied. 2. It is shown that 5 hours after γ-irradiation, the DNA DSB yield sharply decreases in normal repair conditions, while in the presence of the modifiers, not only does it remain but even slightly increases. 3. A nonlinear character of the dose – effect dependence has been found. 4. A linear dependence has been found of DNA fragmentation values on the irradiation dose.

The Influence of Modifying Factors on Radiation-Induced Apoptosis in Human Lymphocytes E.V. Baranova, A.V. Boreyko, I.I. Ravnachka, M.G. Saveleva Induction of apoptotic cells 0, 24, and 48 h after irradiation Apoptosis induction after irradiation with γ -rays and accelerated protons in different phases of the cell cycle G0 G1 S G2 Apoptotic cell induction by γ-irradiation and accelerated protons – in the presence of DNA repair inhibitors аrabinosidсytosine (Ara-C) and hydroxyurea (Hu)

Comparative analysis of G 2 and G 0 sensitivity of human peripheral blood lymphocytes to protons and gamma rays E.M.Zaytseva, M. Deperas'Kaminska, P. V. Kutsalo G.V. Mitsyn, A.G. Molokanov, V.N. Gaevsky, A. Wojcik

2. Study of the combined effect of gamma radiation and lipid A obtained from Escherichia coli on the human leukocytes activities

Effect of Low Dose Gamma Irradiation together with Lipid A on the Human Leukocytes Activities In Vitro E. Belyakova, M. Dubnickova, A. Boreyko The influence of lipid A on number of non irradiated and irradiated leukocytes The influence of lipid A on phagocytic activity and phagocytic index of leukocytes The influence of lipid A on lysozyme activity and peroxidase activity of leukocytes

3. Comparative evaluation of the influence of therapeutic proton and carbon beams on human cells based on cytogenetic disorders in peripheral blood lymphocytes

Cytogenetic Analysis of Human Blood Lymphocytes Irradiated in the G 2 Phase of the Cell Cycle at the Therapeutic Proton Beam of the JINR Phasotron R.D. Govorun, E.M. Zaytseva A dose dependence of the mitotic activity of blood lymphocytes irradiated in different phases of the cell cycle with Bragg peak protons. The mitotic activity of human blood lymphocytes at different times after irradiation in the G2 phase of the cell cycle with a dose of 2 Gy. The calculations show that the effectiveness of the therapeutic beam protons as regards the irradiation of proliferating tumor tissues near the Bragg peak can increase up to 1.4 times compared with that in the case of irradiating normal, non-dividing cells along the initial 155 MeV proton beam. Cytogenetic effects of therapeutic beam protons near the Bragg peak taking into account the contribution to the effect of G2 blood lymphocytes compared to that in the case of G0 lymphocytes and to the effect of the initial 155 MeV proton beam and 60Co X-rays on lymphocytes in the G0 phase of the cell cycle.

4. Acquisition of new data on the genetic control of the induced mutation process in cells with different levels of the genome organization

Effects of rad53 Mutation on Deletion Induction in Haploid Yeast Saccharomyces Cerevisiae after UV- and γ-Irradiation A. Kokoreva, N. Koltovaya The mutagenic action of damaging agents like UV light and γ rays, which can induce DNA double-strand breaks (DSB) and, as consequences, DNA deletions occurring in the process of DSB repair was studied. It is shown that the deletions detected in this system are formed by illegitimate recombination. The effect of the checkpoint rad53 mutation on the mutation rate. It was shown that UV- and γ- irradiation induce deletion mutations in plasmid DNA with the same efficiency in RAD+ strains

Chromosome Loss Induction by Various Types of Radiation in Saccharomyces Cerevisiae T. Zamyatina, N. Bolonkina, N. Koltovaya Induction of excess chromosome IV loss by γ-irradiation ( 60 Со, 0.7 Gy/min, 1.3 МeV) Induction of chromosome VII loss by heavy ions ( 7 Li, 11 B, and 20 Ne with LET of 17, 45, and 120 KeV/ μm) Induction of excess chromosome VII loss by γ-irradiation ( 60 Со, 0.7 Gy/min, 1.3 МeV) Induction of chromosome loss in chromosome IV disomic strains by UV irradiation Induction of chromosome loss in chromosome VII disomic strains by UV irradiation Results: γ –irradiation induces loss of chromosome IV more efficiently than that of chromosome VII. The efficiency of chromosome loss induction by heavy ions depends on their energy. Chromosome VII loss is induced more efficiently by heavier ions with a greater energy. UV γ –rays induce chromosome loss efficiently. Different chromosomes have different stability. The shorter chromosome VII was more stable.

5. Acquisition of data on the mechanism of cataract induction in mice

Effects of Ionizing Radiation on Lens and Retina K. Muranov, M. Loginova, V. Tronov, T. Feldman, I. Kakorin, Yu. Vinogradova, M. Ostrovsky DNA damage induced by gamma-radiation (14Gy) and accelerated protons (14Gy) were studied. The combination of g-rays and UV induces more pronounced damage to the lens than each of the factors alone. Retina histological sections: gamma-rays Lens Retina 6th month 9th month gamma-rays dose = 2 Gy UV dose = W/М 2 Irradiation time = 15 min, daily The phosphenes phenomenon (“light flashes”) induced by cosmic rays can be initiated in the retina photoreceptor cells. Cataract progression takes place on the ground during the post-flight period of time. We suppose that the post-flight cataract progression could depend on a certain extent of UV irradiation.

6. Mathematical modeling of the mutagenic effect of ionizing radiation with different linear energy transfer on bacterial cells

Modeling Base Excision Repair in Escherichia Coli Bacterial Cells O.V. Belov On the basis of the stochastic approach (Gillespie, 1977), a model describing the key BER processes in E. coli cells involving the Fpg protein has been developed. The model describes the transformation of base lesions into apurinic/apyrimidinic (AP) sites, β-δ-elimination, excision of 5'-terminal deoxyribose phosphate from a pre- incised AP site, and Pol I and DNA ligase activity.

Mathematical Modeling of the SOS Inducing Signal in Escherichia Coli Bacterial Cells Caused by Radiations of Different Linear Energy Transfer S.V. Aksenova, O.V. Belov, A.N. Bugay, A.Yu. Parkhomenko A mathematical model has been developed of the concentration dynamics of the SOS repair system inducing signal in Escherichia coli bacterial cells caused by radiations of different LET. Using a model developed earlier, the yield of the basic pre-mutational lesions has been evaluated quantitatively. Processes have been modeled of the basic repair types leading to the formation of the SOS repair system inducing signal. The results have been obtained concerning inducing signal concentration dynamics in wild-type and UmuDC-mutant Escherichia coli bacterial cells caused by radiations of different LET.

A Stochastic Approach to the Mathematical Modelling of the SOS System in Escherichia Coli Bacterial Cells under Ultraviolet Irradiation А.N. Bugay, М.S. Lyashko, A.Yu. Parkhomenko A stochastic approach to modeling of the SOS response in E. coli bacterial cells under ultraviolet irradiation is considered The effect of the time modulation of the SOS response is simulated The dynamics of primary and secondary DNA lesions and protein complexes of the SOS system is calculated 5 J/m 2 20 J/m 2 5 J/m 2 20 J/m 2 50 J/m 2

7. Dosimetric and physical support of radiobiological experiments at the VBLHEP Nuclotron, FLNR cyclotron U400M and the medical beam of the DLNP Phasotron

Beam Preparation for Proton Therapy of Deep Intracranial Targets. Calculation of Variable Thickness Moderators N.A. Emelianova, S.V. Shvidkij Aim: Calculation of individual deep dose distribution-forming devices that would provide the highest precision of the proton beam and minimize damage to healthy tissues using the developed software. Experiments showed that the error of calculation and fabrication of a variable thickness moderator does not exceed the permissible value. The software developed during this work allows the calculation, modeling, and fabrication of variable thickness moderators for irradiating deep seated targets of complicated shapes. With improvements, it can be operated at the Medical Technology Complex. Proton beam depth – dose distribution Individual boluses and collimators made at the Medical Technology Complex workshops

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