Effect of 80.55 MeV/u(12)C(6+) ions on radiosensitivity and cell cycle of human hepatoma cell lines

In this paper, the relationship between radiosensitivity, cell cycle alteration and the change of apoptosis in different human hepatoma cell lines irradiated by heavy ions were studied with the aim of building up the base data for clinical therapy. Exponentially growing hepatoma cell lines were irradiated by 80.55 MeV/u(12)C(6+) ions at a dose of 0 Gy, 0.5 Gy, 1 Gy, 2 Gy, 4 Gy and 8 Gy. The radiosensitivity was assessed by means of the colony-forming assay. The DNA content, the percentage of each cell-cycle phase and the apoptosis rate were obtained with flow cytometry methods. After the irradiation, the SF2 (survival fraction at 2 gray) of SMMC-7721 cells were evidently lower than that of HepG2 cells. The S phase arrest, G2/M phase arrest delay and the apoptosis in the two hepatoma cell lines varied with the increase of the dose and repair time. The heavy ions could obviously kill the human hepatoma cell lines. Compared to HepG2 cells, SMMC-7721 cells were more radiosensitive to C-12(6+) ions.

Induction of cytogenetic adaptive response in spermatogonia and spermatocytes by pre-exposure of mouse testis to low-dose C-12(6+) ions

To investigate the effects of pre-exposure of mouse testis to low-dose C-12(6+) ions on cytogenetics of spermatogonia and spermatocytes induced by subsequent high-dose irradiation. the testes of outbred Kun-Ming strain mice were irradiated with 0.05 Gy of C-12(6+) ions as the pre-exposure dose, and then irradiated with 2 Gy as challenging dose at 4 h after per-exposure. Poly(ADP-ribose) polymerase (PARPs) activity and PARP-1 protein expression were respectively measured by using the enzymatic and Western blot assays at 4 h after irradiation; chromosomal aberrations in spermatogonia and spermatocytes were analyzed by the air-drying method at 8 h after irradiation. The results showed that there was a significant increase in the frequency of chromosomal aberrations and significant reductions of PARP activity and PARP-1 expression level in the mouse testes irradiated with 2 Gy of C-12(6+) ions. However, pre-exposure of mouse testes to a low dose of C-12(6+) ions significantly increased PARPs activity and PARP-1 expression and alleviated the harmful effects induced by a subsequent high-dose irradiation. PARP activity inhibitor 3-aminobenzamide (3-AB) treatment blocked the effects of PARP-1 on cytogenetic adaptive response induced by low-dose C-12(6+) ion irradiation. The data suggest that pre-exposure of testes to a low dose of heavy ions can induce cytogenetic adaptive response to subsequent high-dose irradiation. The increase of PARP-1 protein induced by the low-dose ionizing irradiation may be involved in the mechanism of these observations. (C) 2008 Elsevier B.V. All rights reserved.

Pre-irradiation with low-dose C-12(6+) beam significantly enhances the efficacy of AdCMV-p53 gene therapy in human non-small lung cancer

The combination of ionizing radiation and gene therapy has been investigated. However, there are very few reports about the combination of heavy-ion irradiation and gene therapy. To determine if the pre-exposure to low-dose heavy ion beam enhances the suppression of AdCMV-p53 on non-small lung cancer (NSLC), the cells pre-irradiated or non-irradiated were infected with 20, 40 MOI of AdCMV-p53. Survival fraction and the relative biology effect (RBE) were determined by clonogenic assay. The results showed that the proportions of p53 positive cells in C-12(6+) beam induced AdCMV-p53 infected cells were more than 90%, which were significantly more than those in gamma-ray induced AdCMV-p53 infected cells. The pre-exposure to low-dose 12C6+ beam significantly prevented the G(0)/G(1) arrest and activated G(2)/M checkpoints. The pre-exposure to C-12(6+) beam significantly improved cell to apoptosis. RBEs for the C-12(6+)+ AdCMV-p53 infection groups were 30%-60%,20% -130% and 30%-70% more than those for the C-12(6+)_irradiated only, AdCMV-p53 infected only, and gamma-irradiation induced AdCMVp53 infected groups, respectively. The data suggested that the pre-exposure to low-dose C-12(6+) beam significantly promotes exogenous p53 expression in NSLC, and the suppression of AdCMV-p53 gene therapy on NSLC.

Optical absorption spectra of Na-5, Na-6 and Na-7 clusters: a theoretical study

In the frame of time-dependent density functional theory, the: dynamical polarizabilities of Na-5, Na-6 and Na-7 clusters are calculated using a time-dependent local density approximation. By using Fourier transformation, the optical absorption spectra of Na-5, Na-6 and Na-7 clusters are obtained from their dynamical polarizabilities. It is shown that experimentally measured optical absorption spectra of Na-5, Na-6 and Na-7 clusters are reproduced in our calculations. Furthermore, the calculations of Na-6 and Na-7 clusters are in good agreement with the results of configuration interaction method. Compared with the three-dimensional structure of Na-6, the calculated optical absorption spectra of Na-6 with the two-dimensional structure are more close to the experimental data.

Multi-electron processes in 4.15-11.08 keV/u(13)C(6+) on argon collisions

The relative partial cross sections for C-13(6+)-Ar collisions at 4.15-11.08 keV/u incident energy are measured. The cross-section ratios sigma(2E)/sigma(SC), sigma(3E)/sigma(SC), sigma(4E)/sigma(SC) and sigma(5E)/sigma(SC) are approximately the constants of 0.51 +/- 0.05, 0.20 +/- 0.03, 0.06 +/- 0.03 and 0.02 +/- 0.01 in this region. The significance of the multi-electron process in highly charged ions (HCIs) with argon collisions is demonstrated (sigma(ME)/sigma(SC) as high as 0.79 +/- 0.06). In multi-electron processes, it is shown that transfer ionization is dominant while pure electron capture is weak and negligible. For all reaction channels, the cross-sections are independent of the incident energy in the present energy region, which is in agreement with the static characteristic of classic models, i.e. the molecular Coulomb over-the-barrier model (MCBM), the extended classical over-the-barrier (ECBM) and the semiempirical scaling laws (SL). The result is compared with these classical models and with our previous work of C-13(6+)-Ne collisions

Adaptive hormetic response of pre-exposure of mouse brain with low-dose C-12(6+) ion or Co-60 gamma-ray on growth hormone (GH) and body weight induced by subsequent high-dose irradiation

The brain of the Kun-Ming strain mice were irradiated with 0.05 Gy of C-12(6+) ion or Co-60 gamma-ray as the pre-exposure dose, and were then irradiated with 2 Gy of 12C6+ ion or Co-60 gamma-ray as challenging irradiation dose at 4 h after per-exposure. Body weight and serum growth hormone (GH) concentration were measured at 35th day after irradiation. The results showed that irradiation of mouse brain with 2 Gy of C-12(6+) ion or Co-60 gamma-ray significantly diminished mouse body weight and level of serum GH. The relative biological effectiveness values of a 2 Gy dose of C-12(6+) ion calculated with respect to Co-60 gamma-ray were 1.47 and 1.34 for body weight and serum GH concentration, respectively. Pre-exposure with a low-dose (0.05 Gy) of C-12(6+) ion or Co-60 gamma-ray significantly alleviated reductions of mouse body weight and level of serum GH induced by a subsequent high-dose (2 Gy) irradiation. The data suggested that low-dose ionizing irradiation can induce adaptive hormetic responses to the harmful effects of pituitary by subsequent high-dose exposure.

Germ cell loss induced by C-12(6+) ion irradiation in young female mice

The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of C-12(6+) ion in the Bragg peak or the plateau region. At 10th day after irradiation, ovarian and uterine weights were measured: normal and atretic (identified with the oocyte to be degenerating or absent) primordial, primary and preantral follicles were identified in the largest cross-section of each ovary. Percentage (%) of normal follicles of each developmental stage of oogenesis was calculated. The data showed that compared to controls, there was a dose-related decrease in percentage of normal follicles in each developmental stage. And the weights of ovary and uterus were also reduced with doses of irradiation. Moreover, these effects were much more significant in the Bragg peak region and the region close to the Bragg peak than in the beam's entrance (the plateau region). Radiosensitivity varied in different follicle maturation stages. Primordial follicles, which are thought to be extremely sensitive to ionizing irradiation, were reduced by 86.6%, while primary and preantral follicles reduced only by 72.5% and 61.8% respectively, by exposure with 6 Gy of C-12(6+) ion in the Bragg peak region and the region close to the Bragg peak. The data suggested that due to their optimal depth-dose distribution in the Bragg peak region, heavy ions are ones of the best particles for radiotherapy of tumors located next of vital organs or/and surrounded by normal tissues, especially radiosensitive tissues such as gonads.

Multi-electron processes in C-13(6+) ions with neon collisions in energy region 4.15-11.08 keV/u

The cross-section ratios of double-, triple-, quadruple-, and the total multi-electron processes to the single electron capture process sigma(DE)/sigma(SC), sigma(TE)/sigma(SC), sigma(QE)/sigma(SC) and sigma(ME)/sigma(SC)) as well as the relative ratios among reaction channels in double-electron active, triple-electron active and quadruple- electron active are measured in C-13(6+) -Ne collision in the energy region of 4.15-11.08 keV/u by employing position-sensitive and time-of-flight coincident techniques. It is determined that the cross-section ratios sigma(DE)/sigma(SC), sigma(TE)/sigma(SC), sigma(QE)/sigma(SC) and sigma(ME)/sigma(SC) are approximately the constants of 0.20 +/- 0.03, 0.16 +/- 0.04, 0.06 +/- 0.02 and 0.42 +/- 0.05. These values are obviously smaller than the predictions of the molecular Coulomb over-the-barrier model (MCBM) [J. Phys. B 23 (1990) 4293], the extended classical over-the-barrier model (ECBM) [J. Phys. B 19 (1986) 2925] and the semiempirical scaling laws (SL) [Phys. Rev. A 54 (1996) 4127]. However, the relative ratios among partial processes of DE, TE and QE are found to depend on collision energy, which suggests that the collision dynamics depends on the collision velocity. The limitation of velocity-independent character of ECBM, MCBM and SL is undoubtedly shown.

Evaluation of sex specificity on oxidative stress induced in lungs of mice irradiated by C-12(6+) ions

The aim of this work is to identify if there is sex specificity on C-12(6+) ion-induced oxidative damage in mouse lung at different time points. Kun-Ming mice were divided into two groups, each composed of six males and six females: control group and irradiation group with a single acute dose of 4 Gy. Animals were sacrificed at 2, 4 and 12 h respectively, there lungs were removed immediately, and the oxidative stress-related biomarkers were measured by Diagnostic Reagent Kits. The results showed that the relative activities of superoxide dismutase (4 h), catalase (2 h) and Se-dependent glutathione peroxidase (12 h) have significant changes (P < 0.05) between male groups and female groups, suggesting that the lungs of male mice are more sensitive to counteracting the oxidative challenge. Moreover, higher levels of malondiadehyde and lower contents of glutathione were also found in males, indicating that oxidative stress induced by C-12(6+) ion is pronounced in the lungs of males. We thought that these sex-responded differences may be attributed to the influence of sex hormones.

两种保护剂对C离子诱导小鼠急性肝损伤的应答；Response of Two Protective Agents to Acute Injury Induced by ~(12)C~(6+) Ions in Mouse Liver

比较了N-乙酰半胱氨酸(NAC)及乙酰左旋肉毒碱(ALCAR)对12C6+离子照射小鼠的损伤效应,并探讨了其可能的作用机制。利用4Gy剂量的12C6+离子束对预先给予NAC(100mg/kg)和ALCAR(100mg/kg)保护的昆明小鼠进行单次全身照射。随后检测肝组织中总抗氧化能力(TAC)、DNA单链断裂和细胞凋亡率。结果显示,与照射对照组相比,提前给予NAC和ALCAR均极显著地增强了肝组织的抗氧化能力(P<0.001),减轻了12C6+离子导致的肝组织中DNA断裂(P<0.001)和细胞凋亡(P<0.001)。此外,还发现ALCAR组抗重离子辐照损伤的能力显著地高于NAC组(P<0.05)。实验结果提示了NAC和ALCAR可通过抵御组织内的氧化胁迫,阻止DNA链的断裂和细胞的凋亡,实现对C离子辐照损伤的保护效应。而且ALCAR比NAC可能更适合成为有潜力、有希望的抗C重离子辐射药物。

阿佛曼链霉菌的~(12)C离子辐照效应及高产菌株选育；Research on Mutation Breeding of High-producing Strains from Streptomyces Avermitilis Irradiated by Ion Beam of ~(12)C~(6+)

选用12C6+离子辐照诱变阿维菌素B1a产生菌ZJAV-A1,研究其诱变效应。实验结果表明,12C6+离子辐照剂量50Gy时致死率97%,正突变率最高可达到34.2%。通过12C6+离子诱变处理,结合平板培养基及斜面培养基的正突变菌株筛选,最终获得一株稳定性良好,阿维菌素B1a组分产量稳定在4460—4588μg/ml之间,较出发菌株提高11.1%—14.7%的突变株ZJAV-Y1-203。

Shell effect on stabilization processes following multi-electron transfer in slow Arq+-Ar (g=6-9, 11) collisions

We experimentally investigate the shell effect on the stabilization processes following the multi-electron transfer in slow collisions of Arq+-Ar (q = 6-9, It) The relative cross-section ratios of multi-electron transfer and of the subsequent stabilization with respect to single-electron capture are measured meanwhile compared with the theoretical results predicted by the classical over-barrier model. Our result indicates that the multi-electron transfer is dominant when the projectile charge is large and the subsequent stabilization shows a dramatic variation if the projectile L-shell configuration becomes open. It shows that the subsequent stabilization processes of multiply excited scattering ions have a strong dependence on the projectile shell. (C) 2010 Elsevier BV All rights reserved.

Early effects of low dose C-12(6+) ion or X-ray irradiation on human peripheral blood lymphocytes

The aim of this study was to estimate the acute effects of low dose C-12(6+) ions or X-ray radiation on human immune function. The human peripheral blood lymphocytes (HPBL) of seven healthy donors were exposed to 0.05 Gy C-12(6+) ions or X-ray radiation and cell responses were measured at 24 h after exposure. The cytotoxic activities of HPBL were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT); the percentages of T and NK cells subsets were detected by flow cytometry; mRNA expression of interleukin (IL)-2, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were examined by real time quantitative RT-PCR (qRT-PCR); and these cytokines protein levels in supematant of cultured cells were assayed by enzyme-linked immunosorbent assays (ELISA). The results showed that the cytotoxic activity of HPBL, mRNA expression of IL-2, IFN-gamma and TNF-alpha in HPBL and their protein levels in supernatant were significantly increased at 24 h after exposure to 0.05 Gy C-12(6+) ions radiation and the effects were stronger than observed for X-ray exposure. However, there was no significant change in the percentage of T and NK cells subsets of HPBL. These results suggested that 0.05 Gy high linear energy transfer (LET) C-12(6+) radiation was a more effective approach to host immune enhancement than that of low LET X-ray. We conclude that cytokines production might be used as sensitive indicators of acute response to LDL (C) 2009 COSPAR. Published by Elsevier Ltd. All rights reserved.

2.6 s isomer of Nd-129

Nd-129 was produced by irradiation of an enriched target of Ru-96 with a Ar-36 beam and studied by using a helium-jet fast tape transport system in combination with X-gamma and gamma-gamma coincidence measurements. A 2.6s isomer of Nd-129 was observed for the first time and tentatively proposed to be the configuration of 1/2[411].

Elastic Scattering of He-6 + p at 82.3 MeV/nucleon

Differential cross sections for the elastic scattering of halo nucleus He-6 on proton target were measured at 82.3 MeV/u. The experimental results are well reproduced by optical model calculations using global potential KD02 with a reduction of the depth of real volume part by a factor of 0.7. A systematic analysis shows that this behavior might be related to the weakly bound property of unstable nuclei.