Equivalency of the quality of sublethal lesions after photons and high-linear energy transfer ion beams

The quality of the sublethal damage (SLD) after irradiation with high–linear energy transfer (LET) ion beams was investigated with low-LET photons. Chinese hamster V79 cells and human squamous carcinoma SAS cells were first exposed to a priming dose of different ion beams at different LETs at the Heavy Ion Medical Accelerator in the Chiba facility. The cells were kept at room temperature and then exposed to a secondary test dose of X-rays. Based on the repair kinetics study, the surviving fraction of cells quickly increased with the repair time, and reached a plateau in 2–3 h, even when cells had received priming monoenergetic high-LET beams or spread-out Bragg peak beams as well as X-ray irradiation. The shapes of the cell survival curves from the secondary test X-rays, after repair of the damage caused by the high-LET irradiation, were similar to those obtained from cells exposed to primary X-rays only. Complete SLD repairs were observed, even when the LET of the primary ion beams was very high. These results suggest that the SLD caused by high-LET irradiation was repaired well, and likewise, the damage caused by the X-rays. In cells where the ion beam had made a direct hit in the core region in an ion track, lethal damage to the domain was produced, resulting in cell death. On the other hand, in domains that had received a glancing hit in the low-LET penumbra region, the SLD produced was completely repaired

Selective Effects of Emi1 Depletion in Cancer

Background: To improve the effectiveness of chemo- and radiotherapy only in cancer tissue is important for avoiding side effects. Results: Emi1 depletion enhanced the sensitivity of anticancer reagents and X-ray irradiation in cancer cells. Conclusion: Emi1 siRNA would be a useful new modality for enhancing the effect of chemo- and radiotherapy in various tumors. Significance: This work provides new insights regarding synergistic effect of Emi1 knockdown in combination therapies

High LET Radiation Amplifies Centrosome Overduplication Through a Pathway of γ-Tubulin Monoubiquitination.

[Purpose]Radiation induces centrosome overduplication, leading to mitotic catastrophe and tumorigenesis. Because mitotic catastrophe is one of the major tumor cell killing factors in high linear energy transfer (LET) radiation therapy and long-term survivors from such treatment have a potential risk of secondary tumors, we investigated LET dependence of radiation-induced centrosome overduplication and the underlying mechanism. [Methods and Materials]Carbon and iron ion beams (13-200 keV/μm) and γ-rays (0.5 keV/μm) were used as radiation sources. To count centrosomes after IR exposure, human U2OS and mouse NIH3T3 cells were immunostained with antibodies of γ-tubulin and centrin 2. Similarly, Nbs1-, Brca1-, Ku70-, and DNA-PKcs-deficient mouse cells and their counterpart wild-type cells were used for measurement of centrosome overduplication. [Results]The number of excess centrosome-containing cells at interphase and the resulting multipolar spindle at mitosis were amplified with increased LET, reaching a maximum level of 100 keV/μm, followed by sharp decrease in frequency. Interestingly, Ku70 and DNA-PKcs deficiencies marginally affected the induction of centrosome overduplication, whereas the cell killings were significantly enhanced. This was in contrast to observation that high LET radiation significantly enhanced frequencies of centrosome overduplication in Nbs1- and Brca1-deficient cells. Because NBS1/BRCA1 is implicated in monoubiquitination of γ-tubulin, we subsequently tested whether it is affected by high LET radiation. As a result, monoubiquitination of γ-tubulin was abolished in 48 to 72 hours after exposure to high LET radiation, although γ-ray exposure slightly decreased it 48 hours postirradiation and was restored to a normal level at 72 hours. [Conclusions]High LET radiation significantly reduces NBS1/BRCA1-mediated monoubiquitination of γ-tubulin and amplifies centrosome overduplication with a peak at 100 keV/μm. In contrast, Ku70 and DNA-PKcs deficiencies mitigate centrosome overduplication, although deficiencies of both NBS1/BRCA1 and Ku70/DNA-PKcs markedly enhance cell killing

Dual aspect of radioenhancers and free radical scavengers.

Combining an external beam of ionizing particles with agents to augment the dose effects of cell damages for therapeutic purpose is an important goal of radiotherapy. This last decade intensive works have focused on metal compounds or metal nanoparticles as radiosensitizers to increase the oxidative damages under irradiation. In principle the nanoparticles can be coated with a functionalized shell, to achieve a specific targeting of the tissues, making such approach attractive. The functionalized coating is made of polymers. These molecules are able to scavenge the free radicals, thus, the coating can decrease the overall efficacy of the radiation. The purpose of the present model is to analyse the role of free hydroxyl radicals in the dual behaviour of the added agent. Consideration of the efficiency of the added agents versus the Linear Energy Transfer - LET - of the ionizing particles is made. It is shown that an efficient agent combined with a low-LET particle beams might become less efficient when high-LET particles like heavy-ions are used. These general considerations should be useful to optimize the design of the nanoparticles to be combined with the different kind of ionizing particles

Magneli-Phase Titanium Suboxide Nanocrystals as Highly Active Catalysts for Selective Acetalization of Furfural

Alongside TiO2, Magneli-phase titanium suboxide having the composition of TinO2n-1 is a kind of attractive functional materials composed of titanium. However, there still remain problems to be overcome in the synthesis of titanium suboxide; the existing synthesis methods require high temperature typically over 1000 degrees C and/or postsynthesis purification. This study presents a novel approach to synthesis of titanium suboxide nanoparticles through solid-phase reaction of TiO2 with TiH2. Crystal phases of titanium suboxide were easily controlled by changing TiO2/TiH2 molar ratios in a TiO2-TiH2 mixed precursor, and a series of titanium suboxide nanoparticles including Ti2O3, Ti3O5, Ti4O7, and Ti8O15 were successfully obtained. The reaction of TiO2 with TiH2 proceeded at a relatively low temperature due to the high reactivity of TiH2, giving titanium suboxide nanoparticles without any postsynthesis purification. Ti2O3 nanoparticles and TiO2 were applied as solid acid catalysts for reaction of furfural with 2-propanol. Ti2O3 showed a high catalytic activity and high selectivity for acetalization of furfural, while TiO2 showed only poor activity for transfer hydrogenation of furfural. The difference in catalytic properties is discussed in terms of the acid properties of Ti2O3 and TiO2

Drastic change in selectivity caused by addition of oxygen to the hydrogen stream for the hydrogenation of nitrite in water over a supported platinum catalyst

In the present study, we investigated the influence of the addition of O₂ to the H₂ reactant stream during the hydrogenation of NO₂⁻ in water on the catalytic performances of Al₂O₃-supported precious metal catalysts including Pd, Pt, Ir, Rh, and Ru with 0.3 mmol g-¹ of the metal. Pd/Al₂O₃ showed high selectivity for N₂ irrespective of the presence and absence of O₂, and Rh and Ru/Al₂O₃ were inactive towards the hydrogenation of NO₂⁻ even in the absence of O₂. In contrast, while Pt/Al₂O₃ showed high selectivity for NH₃ (90%) in the absence of O₂ (P-H2 = 0.2 atm and P-O2 = 0 atm), the product drastically changed to N₂ with 93% selectivity when O₂ was added (P-H2 = 0.2 atm and P-O2 = 0.1 atm). Since Pt/Al₂O₃ was completely inactive towards the oxidation of NH₃ with O₂ in water under the reaction conditions, oxidative decomposition of the formed NH₃ was not the reason for the high selectivity for N₂ in the presence of O₂. Kinetic analysis of the reaction in the absence and presence of O₂ and studies on the effects of the Pt size suggested that hydrogen atoms activated on the Pt particles were mainly consumed by O₂ upon H₂O formation in the presence of O₂. We concluded that the inactivation of the Pt sites active for NH₃ formation and furthermore the change in the function of the sites to N₂ formation caused by the O₂ addition lead to the drastic change in the selectivity from NH₃ to N₂ in the presence of O₂

High LET Radiation Amplifies Centrosome Overduplication Through a Pathway of gamma-Tubulin Monoubiquitination.

PURPOSE: Radiation induces centrosome overduplication, leading to mitotic catastrophe and tumorigenesis. Because mitotic catastrophe is one of the major tumor cell killing factors in high linear energy transfer (LET) radiation therapy and long-term survivors from such treatment have a potential risk of secondary tumors, we investigated LET dependence of radiation-induced centrosome overduplication and the underlying mechanism.\nMETHODS AND MATERIALS: Carbon and iron ion beams (13-200 keV/um) and gamma-rays (0.5 keV/um) were used as radiation sources. To count centrosomes after IR exposure, human U2OS and mouse NIH3T3 cells were immunostained with antibodies of gamma-tubulin and centrin 2. Similarly, Nbs1-, Brca1-, Ku70-, and DNA-PKcs-deficient mouse cells and their counterpart wild-type cells were used for measurement of centrosome overduplication.\nRESULTS: The number of excess centrosome-containing cells at interphase and the resulting multipolar spindle at mitosis were amplified with increased LET, reaching a maximum level of 100 keV/um, followed by sharp decrease in frequency. Interestingly, Ku70 and DNA-PKcs deficiencies marginally affected the induction of centrosome overduplication, whereas the cell killings were significantly enhanced. This was in contrast to observation that high LET radiation significantly enhanced frequencies of centrosome overduplication in Nbs1- and Brca1-deficient cells. Because NBS1/BRCA1 is implicated in monoubiquitination of gamma-tubulin, we subsequently tested whether it is affected by high LET radiation. As a result, monoubiquitination of gamma-tubulin was abolished in 48 to 72 hours after exposure to high LET radiation, although gamma-ray exposure slightly decreased it 48 hours postirradiation and was restored to a normal level at 72 hours.\nCONCLUSIONS: High LET radiation significantly reduces NBS1/BRCA1-mediated monoubiquitination of gamma-tubulin and amplifies centrosome overduplication with a peak at 100 keV/um. In contrast, Ku70 and DNA-PKcs deficiencies mitigate centrosome overduplication, although deficiencies of both NBS1/BRCA1 and Ku70/DNA-PKcs markedly enhance cell killing

The Chemopreventive Flavonoid Apigenin Confers Radiosensitizing Effect in Human Tumor Cells Grown as Monolayers and Spheroids

Apigenin, a common dietary flavonoid present in many fruits and vegetables, is a nonmutagenic chemopreventive agent. In the present study, we investigated the effect of apigenin on the radiosensitivity of SQ-5 cells, which are derived from a human lung carcinoma. Actively growing cells were incubated for 16 h at 37 degrees in medium containing 40 micro M apigenin. The cells were then irradiated with X-rays and incubated with apigenin for a further 8 h. Radiosensitivity was assessed using a clonogenic assay. Apoptosis and necrosis were assessed using acridine orange/ethidium bromide double staining. Cells incubated with apigenin exhibited significantly greater radiosensitivity and apoptosis levels than cells not incubated with apigenin. Protein levels were measured by Western blotting. Incubation with apigenin increased protein expression of WAF1/p21 and decreased protein expression of Bcl-2. Furthermore, apigenin sensitized SQ-5 spheroids (cell aggregates growing in a three-dimensional structure that simulate the growth and microenvironmental conditions of in vivo tumors) to radiation. Thus, apigenin appears to be a promising radiosensitizing agent for use against human carcinomas