Adenovirus-mediated p53 gene transfer sensitizes hepatocellular carcinoma cells to heavy-ion radiation

Background. The purpose of this study was to investigate whether adenovirus-mediated p53 transfer could sensitize hepatocellular carcinoma to heavy-ion irradiation. Methods. HepG2 cells were preexposed to a C-12(6+) beam, and then infected with replication-deficient adenovirus recombinant vectors containing human wild-type p53 (AdCMV-p53) (C-12(6+) irradiation + AdCMV-p53 infection). The survival fraction was determined by clonogenic assay. The cell cycle, cell apoptosis, and p53 expression were monitored by flow cytometric analysis. Results. p53 expression in C-12(6+) irradiation + AdCMV-p53 infection groups was markedly higher than that in C-12(6+) irradiation only groups (P < 0.05), suggesting that the preexposure to the C-12(6+) beam promoted the expression of exogenous p53 in HepG2 cells infected with AdCMV-p53 only. The G(1)-phase arrest and cell apoptosis in the C-12(6+) irradiation + AdCMV-p53 infection groups were significantly more than those in the C-12(6+) irradiated groups (P < 0.05). The survival fractions of the C-12(6+) irradiation + AdCMV-p53 infection groups decreased by 30%-49% compared with those of the C-12(6+) beam-irradiated only groups (P < 0.05). Conclusions. Adenovirus-mediated p53 gene transfer can promote G(1)-phase arrest and cell apoptosis, thus sensitizing hepatocellular carcinoma cells to heavy-ion irradiation.

Color center formation in alpha-Al2O3 induced by high energy heavy ions

Single crystals of alpha-alumina were irradiated at room temperature with 1.157 (GeVFe)-Fe-56, 1.755 (GeVXe)-Xe-136 and 2.636 (GeVU)-U-238 ions to fluences range from 8.7 x 10(9) to 6 x 10(12) ions/cm(2). Virgin and irradiated samples were investigated by ultraviolet visible absorption measurements. The investigation reveals the presence of various color centers (F, F+, F-2(2+), F-2(+) and F-2 centers) appearing in the irradiated samples. It is found that the ratio of peak absorbance of F-2 to F centers increases with the increase of the atomic numbers of the incident ions from Fe, Xe to U ions, so do the absorbance ratio of F-2(2+) to F+ centers and of large defect cluster to F centers, indicating that larger defect clusters are preferred to be produced under heavier ion irradiation. Largest color center production cross-section was found for the U ion irradiation. The number density of single anion vacancy scales better with the energy deposition through processes of nuclear stopping, indicating that the nuclear energy loss processes determines the production of F-type defects in heavy ion irradiated alpha-alumina.

Correlation between initial chromatid damage and survival of various cell lines exposed to heavy charged particles

The biophysical characteristics of heavy ions make them a rational source of radiation for use in radiotherapy of malignant tumours. Prior to radiotherapy treatment, a therapeutic regimen must be precisely defined, and during this stage information on individual patient radiosensitivity would be of very great medical value. There are various methods to predict radiosensitivity, but some shortfalls are difficult to avoid. The present study investigated the induction of chromatid breaks in five different cell lines, including one normal liver cell line (L02), exposed to carbon ions accelerated by the heavy ion research facility in Lanzhou (HIRFL), using chemically induced premature chromosome condensation (PCC). Previous studies have reported the number of chromatid breaks to be linearly related to the radiation dose, but the relationship between cell survival and chromatid breaks is not clear. The major result of the present study is that cellular radiosensitivity, as measured by D-0, is linearly correlated with the frequency of chromatid breaks per Gy in these five cell lines. We propose that PCC may be applied to predict radiosensitivity of tumour cells exposed to heavy ions.

Flipped symmetry potential in heavy-ion collisions

Within the IBUU transport model, flipping of the symmetry potential in heavy-ion collisions is studied. It is found that there exist flipping of the symmetry potential in the isospin fractionation, the single neutron to proton ratio, the double neutron to proton ratio and the neutron-proton differential flow from lower to higher incident energies. The flipping of the symmetry potential results from the change of the relative magnitude of the hard and soft symmetry energies at lower and higher densities. Future observations of the flipped symmetry potential in experiment will help the study of the density-dependent symmetry energy.

Conformal irradiation to moving targets in heavy ion radiotherapy with raster-scanning beam delivery system: (II) feasibility experiments

Within the framework of the pilot heavy-ion therapy facility at GSI equipped with an active beam delivery system of advanced raster scanning technique, a feasibility study on actively conformal heavy-ion irradiation to moving tumors has been experimentally conducted. Laterally, real-time corrections to the beam scanning parameters by the raster scanner, leading to an active beam tracing, compensate for the lateral motion of a target volume. Longitudinally, a mechanically driven wedge energy degrader (called depth scanner) is applied to adjust the beam energy so as to locate the high-dose Bragg peak of heavy ion beam to the slice under treatment for the moving target volume. It has been experimentally shown that compensations for lateral target motion by the raster scanner and longitudinal target shift by the depth scanner are feasible.

Particle transfer and fusion cross-section for super-heavy nuclei in dinuclear system

Within the dinuclear system (DNS) conception, instead of solving the Fokker-Planck equation (FPE) analytically, the master equation is solved numerically to calculate the fusion probability of super-heavy nuclei, so that the harmonic oscillator approximation to the potential energy of the DNS is avoided. The relative motion concerning the energy, the angular momentum and the fragment deformation relaxations is explicitly treated to couple with the diffusion process. The nucleon transition probabilities, which are derived microscopically, are related with the energy dissipation of the relative motion. Thus they are time dependent. Comparing with the analytical solution of FPE at the equilibrium, our time-dependent results preserve more dynamical effects. The calculated evaporation residue cross-sections for one-neutron emission channel of Pb-based reactions are basically in agreement with the known experimental data within one order of magnitude.

Study on dynamic fusion barrier in heavy-ion fusion reactions

By means of the improved quantum molecular dynamics model, the incident energy dependent dynamical fusion potential barriers for heavy nucleus reaction systems are investigated. It is found that with decrease of incident energy the lowest dynamic barrier is obtained which approaches to the adiabatic static barrier and with increase of the incident energy the dynamic barrier goes up to the diabatic static barrier. Based on the dynamical study a microscopic understanding of the extra-push in fusion reactions of heavy systems and a new explanation of tunneling process for the fusion at the incident energy below the static and above the lowest dynamic barrier are presented. In order to understand the energy dependence of the dynamical barrier we also pay a great attention to study the neck formation and shape deformation during the dynamic lowering of the barrier.

Single and double pi(-)/pi(+) ratios in heavy-ion reactions as probes of the high-density behavior of the nuclear symmetry energy

Based on the isospin- and momentum-dependent hadronic transport model IBUU04, effects of the nuclear symmetry energy on the single and double pi(-)/pi(+) ratios in central reactions of Sn-132+Sn-124 and Sn-112+Sn-112 at a beam energy of 400 MeV/nucleon are studied. It is found that around the Coulomb peak of the single pi(-)/pi(+) ratio the double pi(-)/pi(+) ratio taken from the two isotopic reactions retains about the same sensitivity to the density dependence of nuclear symmetry energy. Because the double pi(-)/pi(+) ratio can significantly reduce the systematic errors, it is thus a more effective probe for the high-density behavior of the nuclear symmetry energy.

Melting of Au and Al in nanometer Fe/Au and Fe/Al multilayers under swift heavy ions: A thermal spike study

Knowing that Fe is sensitive to swift heavy ion irradiations whereas Au and Al are not, the behavior of nanometric metallic multilayer systems, like [Fe(3 nm)/Au(x)](y) and [Fe(3 nm)/Al(x)](y) with x ranging between 1 and 10 mn, were studied within the inelastic thermal spike model. In addition to the usual cylindrical geometry of energy dissipation perpendicular to the ion projectile direction, the heat transport along the ion path was implemented in the electronic and atomic sub-systems. The simulations were performed using three different values of linear energy transfer corresponding to 3 MeV/u of Pb-208, Xe-132 and Kr-84 ions. For the Fe/Au system, evidence of appearance of a molten phase was found in the entire Au layer, provided the Au thickness is less than 7 nm and 3 nm for Pb and Xe ions, respectively. For the Fe/Al(x) system irradiated with Pb ions, the Al layers with a thickness less than 4 nm melt along the entire ion track. Surprisingly, the Fe layer does not melt if the Al thickness is larger than 2 nm, although the deposited energy surpasses the electronic stopping power threshold of track formation in Fe. For Kr ions melting does not occur in any of the multilayer systems.

Materials research with swift heavy ions at the IMP accelerators

The main ion beams acceleration facilities and research fields of the Institute of Modern Physics (IMP) are briefly introduced. Some of the experimental instruments, typical works and the obtained results on the materials research with swift heavy ions at the IMP-accelerators are presented.

Radiobiological response of human hepatoma and normal liver cells exposed to carbon ions generated by Heavy Ion Research Facility in Lanzhou

Human hepatoma and normal liver cells were irradiated with C-12(6+), ion beams (LET= 96.05 keV/mu m) and gamma-rays at Heavy Ion Research Facility in Lanzhou (HIRFL). The chromatid breaks and break types were detected using the premature chromosome condensation technique. Our experimental results showed that chromatid breaks seem to have a good relation with C-12(6+) absorbed dose and C-12(6+) are more effective to induce chromatid breaks as compared to they-rays. For C-12(6+) ion irradiation the major break was isochromatid break, while chromatid breaks were dominant for gamma-ray irradiation. We also observed that the Relative Biology Effectiveness (RBE) of C-12(6+) ion is about 2.5 times higher than that of gamma-rays.

Development of the lanzhou heavy ion linac

The heavy ion linac in Lanzhou is designed as a future injector for the Cooling Storage Ring (CSR). In order to keep the total machine within 40 meters, the IH (Interdigital H-type) structure is adopted for its higher acceleration gradient compared with the traditional DTL structure. The designed minimum charge over mass ratio is 1/6, the output energy is 16MeV/u and the beam current is 1A.mu A. The RFQ and the first DTL tank will work at 100MHz, and the other DTL tanks will work at the double frequency. The design criteria, main parameters and the detailed beam dynamic design are introduced in this paper.

Nuclear reaction dynamics induced by halo-nuclei at intermediate energy heavy ion collisions

We studied systematically the reaction dynamics induced by neutron-halo nuclei and proton-halo nuclei within the isospin dependent quantum molecular dynamics, such as the effects of loose bound halo-nuclei on the fragmentation reaction and momentum dissipation for different colliding systems with different beam energies and different impact parameters. In order to emphasize the roles of neutron-halo nucleus B-19 and proton-halo nucleus Al-23 on the reaction dynamics we also calculated the the reaction dynamics induced by the stable nuclei F-19 and Na-23 with equal mass under identical incident channel conditions. Based on the comparison of results of reaction dynamics induced by halo-nucleus colliding systems and stable nucleus collidinmg systems we found that the roles of loose bound halo-nucleus structure on the fragmentation multiplicity and nuclear stopping (momentum dissipation) are important for all of colliding systems with different beam energies and minor impact parameters, such as, the loose bound halo-nuclei structure increases the fragmentation multiplicity, but reduces the nuclear stopping.

Entrance channel effects on the role of isospin-dependent momentum interaction in isospin fractionation in heavy ion collisions

An isospin degree of freedom is inserted into the momentum dependent interaction in the quantum molecular dynamics model to obtain an isospin dependent momentum interaction given in a form practically usable in isospin dependent quantum molecular dynamics model. We investigate the entrance channel effects for the role of isospin momentum dependent interaction on the isospin fractionation ratio and its dynamical mechanism in the intermediate energy heavy ion collisions. It is found that the isospin dependent momentum interaction induces a significant reduction of isospin fractionation ratio under all entrance channel conditions. However the strong dependence of isospin fractionation ratio on the symmetry potential is preserved after considering the isospin degree of freedom in the momentum dependent interaction.

Radio-resistance induced by nitric oxide to heavy ion irradiation in A172 human glioma cells

To investigate effects of nitric oxide on cellular radio-sensitivity, three human glioma cell lines, i.e. A172, A172 transfected green fluorescence protein (EGFP) gene (EA172) and A172 transfected inducible nitric oxide synthesis (iNOS) gene (iA72), were irradiated by C-12(6+) ions to 0, 1 or My. Productions of nitric oxide and glutathione (GSH) in A172, EA172 and iA172 were determined by chemical methods, cell cycle was analyzed by flow cytometry at the 24th hour after irradiation, and survival fraction of the cells was measured by colorimetric MTT assay at the 5th day after irradiation. The results showed that the concentrations of nitric oxide and GSH in iA172 were significantly higher than in A172 and EA172; the G(2)/M stage arrest induced by the C-12(6+) ion irradiation was observed in A172 and EA172 but not in iA172 at the 24th hour after exposure; and the survival fraction of iA172 was higher than that of EA172 and iA172. Data suggest that the radio-sensitivity of the A172 was reduced after the iNOS gene transfection. The increase of GSH production and the change of cellular signals such as the cell cycle control induced by nitric oxide may be involved in this radio-resistance.