D0 Values Research Articles

Relative biological effectiveness in canine osteosarcoma cells irradiated with accelerated charged particles.

Heavy ions, characterized by high linear energy transfer (LET) radiation, have advantages compared with low LET protons and photons in their biological effects. The application of heavy ions within veterinary clinics requires additional background information to determine heavy ion efficacy. In the present study, comparison of the cell-killing effects of photons, protons and heavy ions was investigated in canine osteosarcoma (OSA) cells in vitro. A total of four canine OSA cell lines with various radiosensitivities were irradiated with 137Cs gamma-rays, monoenergetic proton beams, 50 keV/µm carbon ion spread out Bragg peak beams and 200 keV/µm iron ion monoenergetic beams. Clonogenic survival was examined using colony-forming as says, and relative biological effectiveness (RBE) values were calculated relative to gamma-rays using the D10 value, which is determined as the dose (Gy) resulting in 10% survival. For proton irradiation, the RBE values for all four cell lines were 1.0-1.1. For all four cell lines, exposure to carbon ions yielded a decreased cell survival compared with gamma-rays, with the RBE values ranging from 1.56-2.10. Iron ions yielded the lowest cell survival among tested radiation types, with RBE values ranging from 3.51-3.69 observed in the three radioresistant cell lines. The radiosensitive cell line investigated demonstrated similar cell survival for carbon and iron ion irradiation. The results of the present study suggest that heavy ions are more effective for killing radioresistant canine OSA cells when compared with gamma-rays and protons. This markedly increased efficiency of cell killing is an attractive reason for utilizing heavy ions for radioresistant canine OSA.

Influence of milling parameters on particle size of ulexite material

Commercial raw ulexite (U) materials were milled from 0h to 8h by using mechanical milling technique for various initial powder size (−3mm; −75μm), ball to powder ratio (5:1; 10:1), and ball size (10mm; 5mm). Particle size, morphology, elemental, and crystal structure measurements of the milled powders were performed. In the particle size distribution analysis, the smallest d50 and d10 values were respectively found as 8.846μm and 790nm for U_5m powder (obtained from that initial powder with −3mm in size was milled by balls with 5mm in size) at 0.5h. In the morphology analysis, the microstructure of the U_5m powder was observed to be more homogeneous by means of milling process. In the elemental analysis, it was deduced that the U_5m powder is not a pure compound. In the crystal structure analysis, it was determined that the crystal structure of the U_5m powder is exponentially deteriorated with increasing the milling time, and then it has become an amorphous structure at the end of 8h. The crystalline size of the U_5m powder is reduced to 15.5nm after 4h of milling. The results of this study are considered to be useful for future nano studies and industrial applications of ceramic ulexite compound, which is a boron mineral.

Numb Gene Enhances Radiation Sensitivity of Nonsmall Cell Lung Cancer Stem Cells.

To study the effects of Numb gene expression on radiation sensitivity of nonsmall cell lung cancer (NSCLC) stem cells. The side population (SP) cells A549-SP were transfected with pcDNA3.1 (pcDNA3.1 group), pcDNA-Numb (pcDNA-Numb group) and shRNA-Numb (shRNA-Numb group). Real-time quantitative polymerase chain reaction and Western blot were performed to determine Numb expression; MTT method was used to measure the proliferation activity change of the NSCLC stem cells both before and after irradiation with different doses of 60Coγ ray; Hoechst staining and Annexin V-FITC/PI were used to detect the apoptosis of the NSCLC stem cells; and colony-forming assay was used to determine the effect of Numb expression on radiation sensitivity of the NSCLC stem cells. Increased mRNA and protein expressions of the A549-SP cells were found in the pcDNA-Numb group, and decreased mRNA and protein expressions were found in the shRNA-Numb group. The optical density value of the cells decreased in the pcDNA-Numb group but increased in the shRNA-Numb group. The cells with over-expressed Numb showed obvious nuclear condensation and fragmentation; the apoptosis rate increased significantly. The cells with knockdown Numb showed less nuclear damage; the apoptosis rate significantly decreased. After irradiation, the cells in the pcDNA-Numb group showed decreased survival rate, clonality, and the values of D0, Dq, N, and SF2; whereas the cells in the shRNA-Numb group showed the opposite trend. Radiation sensitivity of NSCLC stem cells was enhanced with the increase of Numb expression. Determination of Numb expression helped to evaluate the response of lung cancer to radiotherapy, which was important for guiding tumor treatment clinically.

ChemInform Abstract: Experimental and Theoretical Determination of Dissociation Energies of Dispersion‐Dominated Aromatic Molecular Complexes

AbstractReview: 305 refs.

Cancer stem cells in radiation resistance of esophageal cancer: role and molecular mechanism

Objective To investigate the role of cancer stem cells in radiation resistance of esophageal cancer and its molecular mechanism, and to provide a theoretical basis for radiotherapy for esophageal cancer. Methods Esophageal cancer cell line TE1 was treated with 8 Gy of radiation. Esophageal cancer cell line with resistance to radiation, TE1-res, was established and screened. Cell counting was used to evaluate cell proliferation. Flow cytometry was used to determine the expression of CD44(high) CD24(-)CD133(+) and apoptosis in cells. The colony formation assay was used to determine the colony-forming rate and cell survival curve. Bisulfite sequencing PCR was used to determine the methylation status of cancer suppressor genes. Comparison of the data was made by group t test or analysis of variance. Results Compared with TE1 cells, TE1-res cells had significantly enhanced proliferation, a significantly higher proportion of CD44(high) CD24(-)CD133(+) cells, and significantly enhanced resistance to apoptosis (mean value 20.84×105vs. 4.46×105/day, P=0.008; (38.0±2.9)% vs. (10.1±1.3)%, P=0.001; mean value 33.23% vs. 10.50%, P=0.003). After treatment with 8 Gy of radiation, TE1-res cells had significantly higher colony-forming rate and D0 value than TE1 cells ((14.3±2.6)% vs. (0.9±0.3)%, P=0.011; 3.28 vs. 2.19 Gy, P=0.125). Moreover, the promoter methylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B was significantly enhanced in TE1-res cells than in TE1 cells ((89.7±4.9)% vs. (5.0±0.5)%, P=0.001; (92.3±4.7)% vs. (10.4±0.7)%, P=0.001; (90.7±3.7)% vs. (7.9±0.4)%, P=0.001; (83.4±5.7)% vs. (17.2±1.2)%, P=0.002; (90.2±6.7)% vs. (4.4±1.2)%, P=0.002). Conclusions Cancer stem cells play an important role in radiation resistance of esophageal cancer. The resistance to radiation is closely associated with promoter hypermethylation in cancer suppressor genes including SPINT2, CDKN1B, DKK1, TP53, and PPP2R1B. Key words: Esophageal neoplasms cell line; Irradioresistance; Cancer suppressor gene; Methylation

Comparative antibacterial activity of topical antiseptic eardrops against methicillin-resistant Staphylococcus aureus and quinolone-resistant Pseudomonas aeruginosa

ObjectiveAural irrigation using antiseptic solutions can be an effective medical treatment of chronic suppurative otitis media (CSOM) owing to the increasing prevalence of antibiotic-resistant CSOM infections. In the present study, we compared the antimicrobial activities of 100% Burow's solution, 50% Burow's solution, 2% acetic acid, vinegar with water (1:1), and 4% boric acid solution against methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), quinolone-resistant Pseudomonas aeruginosa (QRPA), and quinolone-susceptible P. aeruginosa (QSPA) in vitro. MethodsWe examined the antimicrobial activities of five antiseptic solutions against MRSA, MSSA, QRPA, and QSPA. The antimicrobial activities of the solutions were calculated as a percentage of the surviving microorganisms by dividing the viable count in each antiseptic solution with that in control. The time (D10 value) required for each of the five solutions to inactivate 90% of the microorganism population was also investigated. ResultsBurow's solution exhibited the highest antimicrobial activity and the lowest D10 value against MRSA, MSSA, QRPA, and QSPA, followed by 2% acetic acid, vinegar with water (1:1), and 4% boric acid solution. ConclusionOur results indicate that Burow's solution has the most potent activity against bacteria including antibiotic-resistant strains. Twofold dilution of the solution is recommended to avoid ototoxicity.

Experimental and Theoretical Determination of Dissociation Energies of Dispersion-Dominated Aromatic Molecular Complexes

The dissociation energy (D0) of an isolated and cold molecular complex in the gas-phase is a fundamental measure of the strength of the intermolecular interactions between its constituent moieties. Accurate D0 values are important for the understanding of intermolecular bonding, for benchmarking high-level theoretical calculations, and for the parametrization of force-field models used in fields ranging from crystallography to biochemistry. We review experimental and theoretical methods for determining gas-phase D0 values of M·S complexes, where M is a (hetero)aromatic molecule and S is a closed-shell "solvent" atom or molecule. The experimental methods discussed involve M-centered (S0 → S1) electronic excitation, which is often followed by ionization to the M(+)·S ion. The D0 is measured by depositing a defined amount of vibrational energy in the neutral ground state, giving M(‡)·S, the neutral S1 excited state, giving M*·S, or the M(+)·S ion ground state. The experimental methods and their relative advantages and disadvantages are discussed. Based on the electronic structure of M and S, we classify the M·S complexes as Type I, II, or III, and discuss characteristic properties of their respective potential energy surfaces that affect or hinder the determination of D0. Current theoretical approaches are reviewed, which comprise methods based on a Kohn-Sham reference determinant as well as wave function-based methods based on coupled-cluster theory.

The Effect of X-Ray and Heavy Ions Radiations on Chemotherapy Refractory Tumor Cells.

The purpose of this study is to link both numeric and structural chromosomal aberrations to the effectiveness of radiotherapy in chemotherapy refractory tumor cells. Neuroblastoma (LAN-1) and 79HF6 glioblastoma cells derived from patients and their chemoresistant sublines were artificially cultured as neurospheres and irradiated by X-rays and heavy ions sources. All the cell lines were irradiated by Carbon-SIS with LET of 100 keV/μm. However, 79HF6 cells and LAN-1 cells were also irradiated by Carbon-UNILAC with LET of 168 keV/μm and Nickel ions with LET of 174 keV/μm, respectively. The effect of radiation on the survival and proliferation of cells was addressed by standard clonogenic assays. In order to analyze cell karyotype standard Giemsa staining, multicolor fluorescence in situ hybridization (mFISH) and multicolor banding (mBAND) techniques were applied. Relative biological effectiveness values of heavy ion beams relative to X-rays at the D10 values were found between 2.3 and 2.6 with Carbon-SIS and Nickel for LAN-1 and between 2.5 and 3.4 with Carbon-SIS and Carbon-UNILAC for 79HF6 cells. Chemorefractory LAN-1(RETO) cells were found more radioresistant than untreated LAN-1(WT) cells. 79HF6(RETO) glioblastoma cells were found more radiosensitive than cytostatic sensitive cells 79HF6(WT). Sphere formation assay showed that LAN-1(RETO) cells were able to form spheres in serum-free culture, whereas 79HF6 cells could not. Most of 79HF6(WT) cells revealed a number of 71-90 chromosomes, whereas 79HF6(RETO) revealed a number of 52-83 chromosomes. The majority of LAN-1(WT) cells revealed a number of 40-44 chromosomes. mFISH analysis showed some stable aberrations, especially on chromosome 10 as judged by the impossibility to label this region with specific probes. This was corroborated using mBAND analysis. Heavy ion irradiation was more effective than X-ray in both cytostatic naive cancer and chemoresistant cell lines. LAN-1(RETO) chemoresistant neuroblastoma cells were found to be more radioresistant than the cytostatic naive cells (LAN-1(WT)), whereas this effect was not found in 79HF6 cells.

Complete genome sequence of Deinococcus actinosclerus BM2T, a bacterium with Gamma-radiation resistance isolated from soil in South Korea

A Gram-positive, short-rod shaped and non-motile bacterium Deinococcus actinosclerus BM2T, resistant to gamma and UV radiation, was isolated from a soil sample collected in South Korea. Strain BM2T showed high resistance to gamma radiation with D10 value of 9 kGy. The complete genome of D. actinosclerus BM2T consists of a single chromosome (3,264,334bp). The genome features showed the presence of intracellular proteases that help to eliminate radiation-induced ROS during recovery from ionizing radiation damage.

Deinococcus actinosclerus sp. nov., a novel bacterium isolated from soil of a rocky hillside.

Three Gram-stain-positive, catalase- and oxidase-positive coccus- or rod-shaped bacterial strains, designated BM2T, BM4 and BM5, were isolated from soil in South Korea. They showed strong resistance to gamma radiation with a D10 value of 9 kGy but weak UVC resistance. The 16S rRNA sequences of strains BM2T, BM4 and BM5 represent a novel subline within the genus Deinococcus in the family Deinococcaceae. The 16S rRNA gene sequences of strains BM2T, BM4 and BM5 were indistinguishable and showed 98.1-87.3 % similarity with other species of the genus Deinococcus. Strain BM2T exhibited relatively high levels of DNA-DNA hybridization with BM4 (87 ± 0.8 %) and BM5 (92 ± 1.2 %). Meanwhile, it showed a low level of DNA-DNA hybridization ( < 30 %) with other closely related species of the genus Deinococcus. The strains showed the typical chemotaxonomic characteristics of the genus Deinococcus, with the presence of menaquinone 8 as the respiratory quinone; the major fatty acids were summed feature 3 (composed of C16 : 1ω7c/C16 : 1ω6c), C15 : 1ω6c and C16 : 0. The DNA G+C content of strain BM2T was 69.7 mol%. The polar lipid profile included major amounts of phosphatidylglycerol, phosphatidylcholine and an unknown aminolipid. On the basis of phenotypic and genotypic properties, and phylogenetic distinctiveness, strains BM2T, BM4 and BM5 should be classified in a novel species in the genus Deinococcus, for which the name Deinococcus actinosclerus sp. nov. is proposed. The type strain is BM2T ( = KEMB 5401-184T = JCM 30700T); reference strains are BM4 ( = JCM 30701) and BM5 ( = JCM 30702).

Using evolutionary algorithms to determine the residual stress profile across welds of age-hardenable aluminum alloys

This paper presents an evolutionary based method to obtain the un-stressed lattice spacing, d0, required to calculate the residual stress profile across a weld of an age-hardenable aluminum alloy, AA2024. Due to the age-hardening nature of this alloy, the d0 value depends on the heat treatment. In the case of welds, the heat treatment imposed by the welding operation differs significantly depending on the distance to the center of the joint. This implies that a variation of d0 across the weld is expected, a circumstances which limits the possibilities of conventional analytical methods to determine the required d0 profile. The interest of the paper is, therefore, two-fold: First, to demonstrate that the application of an evolutionary algorithm solves a problem not addressed in the literature such as the determination of the required data to calculate the residual stress state across a weld. Second, to show the robustness of the approximation used, which allows obtaining solutions for different constraints of the problem. Our results confirm the capacity of evolutionary computation to reach realistic solutions under three different scenarios of the initial conditions and the available experimental data.

Complete genome sequence of Rufibacter sp. DG31D, a bacterium resistant to gamma and UV radiation toxicity

The ionizing radiation toxicity becomes a major concern for the modern world, recent years, several special interest has been given to the research for the radiation resistant and the mechanisms of which the radiation resistant bacteria survive after the irradiation. In the current study, we have isolated strain DG31D was isolated from gamma ray-irradiated soil sample and showed resistant to gamma and UV radiation. The aim of this study is to understanding the radiation resistant mechanisms and their genomic features of the strain DG31D, which can be potentially used for the biotechnological application to degrade harmful soil contamination near the nuclear power stations and other radiation-affected areas. Strain DG31D showed resistant to UV and gamma radiation with D10 value of 10 kGy. The genome comprised of 4,820,793 bp with the G+C content of 51.4%. It contains the genomic features of enzymes involved in the nucleotide excision repair (NER) pathway that protect the damaged DNA.

Effect of X-irradiation on Citrus Canker Pathogen Xanthomonas citri subsp. citri of Satsuma Mandarin Fruits

Citrus canker caused by Xanthomonas citri subsp. citri (Xcc) is one of the most important bacterial diseases of citrus. Because citrus canker is not found in many countries including European Union and Australia, Xcc is strictly regulated in order to prevent its spread. In this study, the effects of X-irradiation on Xcc growth either in the suspension or on the surface of citrus fruits were investigated. The suspension containing 1×107 cfu/ml of Xcc was irradiated with different absorbed doses of X-irradiation ranging from 50 to 400 Gy. The results showed that Xcc was fully dead at 400 Gy of X-irradiation. To determine the effect of X-irradiation on quarantine, the Xcc-inoculated citrus fruits were irradiated with different X-ray doses at which Xcc was completely inhibited by an irradiation dose of 250 Gy. The D10 value for Xcc on citrus fruits was found to be 97 Gy, indicating the possibility of direct application on citrus quarantine without any side sterilizer. Beside, presence of Xcc on the surface of asymptomatic citrus fruits obtained from citrus canker-infected orchards was noted. It indicated that the exporting citrus fruits need any treatment so that Xcc on the citrus fruits should be completely eliminated. Based on these results, ionizing radiation can be considered as an alternative method of eradicating Xcc for export of citrus fruits.

Limiting diffusion coefficients of sodium octanoate, and octanoic acid in aqueous solutions without and with α-cyclodextrin

The Taylor dispersion technique has been used for measuring limiting binary mutual diffusion coefficients of octanoic acid and sodium octanoate at T=298.15K (D0), respectively, using water as carrier solution, and different injections solutions from (0.75 to 100)·10−3mol⋅dm−3. These D0 values, together with the Stokes–Einstein equation, were used to determine the equivalent hydrodynamic radii, Rh, at infinitesimal concentration of these species (octanoic acid and sodium octanoate). In addition, the limiting diffusion coefficients of the molecular (D0m) and dissociated (D0±) forms of the octanoic acid were estimated.We have also investigated the diffusion properties for a system containing octanoic acid, α-cyclodextrin (α-CD) and water. From these results, we have estimated the percentages of free (C7COOH) and associated forms of octanoic acid (α-CD/C7COOH) and the equilibrium constant, K, for a supramolecular host–guest complex between octanoic acid and α-CD.

Establishment and biological characterization of radiation-resistant lung carcinoma cell lines

Objective To establish radiation-resistant lung carcinoma cell lines, and to investigate the changes in morphology, apoptosis, invasive migration, and epithelial-mesenchymal transition (EMT) in cells. Methods The radiation-resistant lung carcinoma cell lines were obtained by exposure of lung carcinoma cell lines, A549 and H1299, to radiation with a low dose in fractions, a sublethal dose, or a gradually increasing dose. The morphological changes in cells, radiosensitivity, survival rates after exposure, apoptosis rates, changes in invasive migration, and expression of EMT marker proteins were evaluated using microscopy, colony formation assay, CCK-8 assay, flow cytometry, transwell migration assay, and Western blot, respectively. Results Radiation with a gradually increasing dose successfully induced the radiation-resistant cell lines, A549R and H1299R. The morphological study showed that the morphology of radiation-resistant cells was converted to the morphology of mesenchymal cells. Compared with A549 and H1299 cells, the values of D0, Dq, and SF2 were significantly increased in A549R (P=0.017, P=0.001, P=0.000) and H1299R (P=0.033, P=0.000, P=0.008) cells, respectively; the values of α and α/β were significantly reduced in A549R (P=0.018; P=0.007) and H1299R (P=0.001; P=0.009) cells, respectively. The survival rates in A549R and H1299R cells after exposure to radiation with various doses were significantly higher than those in the control groups (all P<0.05). After exposure, the apoptosis rates were significantly reduced in A549R and H1299R cells (P=0.02, P=0.01); the invasion and migration rates were significantly increased in A549R (P=0.000; P=0.001) and H1299R (P=0.001, P=0.002) cells; the expression of E-cadherin was significantly down-regulated in A549R and H1299R cells (P=0.00, P=0.01), while the expression of vimentin was significantly elevated in A549R and H1299R cells (P=0.02, P=0.01). Conclusions The radiation-resistant lung carcinoma cell lines are successfully established. Both cell lines show enhanced invasion and migration, which may be associated with EMT. Key words: Lung carcinoma cell line, radioresistance; Colony formation assay; Transwell cell assay; Epithelial-mesenchymal transition

Effect of RNA interference for MDC1 gene on cell cycle and expression of related proteins in esophageal carcinoma cells after X-ray radiation

Objective To apply RNA interference technique for reducing the expression of MDC1 gene in esophageal carcinoma cell line ECA109, observe the changes in cell cycle and radiosensitivity after radiation, and discuss related mechanisms. Methods Three pairs of effective interference sequences and negative control sequences were synthesized for MDC1 mRNA sequence, and a recombinant plasmid was constructed with the vector pSIH1-H1-copGFP. RT-PCR and Western blot were used to determine the expression levels of MDC1 mRNA and protein. Colony-forming assay was applied to measure radiosensitivity, flow cytometry to determine cell cycle, Western blot to determine the expression of CHK1 and CHK2 proteins, and laser scanning confocal microscope to observe the number of MDC1 blotches inside the nucleus. One-way analysis of variance was used to analyze the differences between groups. Results The pSIH1-H1-copGFP plasmid was constructed successfully and ECA109 cells were infected to obtain ECA109M cells with stable transfection. The expression levels of MDC1 mRNA and protein in ECA109M cells were lower than those in ECA109N and ECA109 cells (P=0.032 and 0.041, respectively). After 5-Gy radiation, ECA109M cells had a lower proportion of G2+ M cells than ECA109N and ECA109 cells (P=0.026). After 5-Gy radiation, ECA109, ECA109N, and ECA109M cells had similar expression levels of CHK1 and CHK2 proteins (P=0.345 and 0.451, respectively), and ECA109M cells had a lower expression level of CHK2 T68 protein than ECA109 and ECA109N cells (P=0.012). ECA109 cells had a D0 value of 3.06 Gy and an SF2 value of 0.91; the D0 values for ECA109N and ECA109M cells were 2.90 Gy and 1.88 Gy, respectively, and the SF2 values for them were 0.89 and 0.84, respectively (P=0.021 and 0.037, respectively). Conclusions RNA interference can reduce the expression levels of MDC1 protein and cell cycle-related proteins, release cell cycle arrest, and enhance radiosensitivity in esophageal carcinoma ECA109 cells. Key words: Esophageal carcinoma; RNA interference; cell cycle protein; MDC1; radiosensitivity

Enhanced Radiation Resistance of Methanosarcina soligelidi SMA-21, a New Methanogenic Archaeon Isolated from a Siberian Permafrost-Affected Soil in Direct Comparison to Methanosarcina barkeri.

Permafrost-affected soils are characterized by a high abundance and diversity of methanogenic communities, which are considered suitable model organisms for potential life on Mars. Methanogens from Siberian permafrost have been proven to be highly resistant against divers stress conditions such as subzero temperatures, desiccation, and simulated thermophysical martian conditions. Here, we studied the radiation resistance of the currently described new species Methanosarcina soligelidi SMA-21, which was isolated from a Siberian permafrost-affected soil, in comparison to Methanosarcina barkeri, which is used as a reference organism from a nonpermafrost soil environment. Both strains were exposed to solar UV and ionizing radiation to assess their limits of survival. Methanosarcina soligelidi exhibit an increase in radiation resistance to UV (2.5- to 13.8-fold) and ionizing radiation (46.6-fold) compared to M. barkeri. The F10 (UVC) and D10 (X-rays) values of M. soligelidi are comparable to values for the well-known, highly radioresistant species Deinococcus radiodurans. In contrast, the radiation response of M. barkeri was highly sensitive to UV and ionizing radiation comparably to Escherichia coli and other radiosensitive microorganisms. This study showed that species of the same genus respond differently to UV and ionizing radiation, which might reflect the adaptation of Methanosarcina soligelidi SMA-21 to the harsh environmental conditions of the permafrost habitat. Methanogenic archaea-Environmental UV-Ionizing radiation-Permafrost-Radiation resistance-Mars.

Complete genome sequence of Deinococcus swuensis, a bacterium resistant to radiation toxicity

Deinococcus swuensis DY59T is a Grampositive, coccus-shaped bacterium. Most members of the genus Deinococcus are able to grow in the presence of high levels of chronic radiation toxicity and desiccation because they can protect enzymes from reactive oxygen species generated during ionizing radiation. The mechanisms behind the resistance to radiation toxicity and the genomic features of resistance could be useful to exploit Deinococcus swuensis in the biotechnological applications such as detoxification of xenobiotic contaminated with radioactive wastes. Strain DY59T showed resistance to gamma radiation with a D10 value (i.e. the dose required to reduce the bacterial population by 10-fold) in excess of 5 kGy. However, the genus Deinococcus is slightly characterized at the genome level, despite its potential importance. Thus, the present study determined the features of Deinococcus swuensis DY59T, as well as its genome sequence and annotation. The genome comprised of 3,531,443 bp with a G + C content of 67.4%, which included 3,305 protein-coding genes and 58 RNA genes. Based on the genome annotation, the strain DY59T undergoes prokaryotic type nucleotide excision repair pathway, restores the damaged gene, and resists the ionizing radiation toxicity.

Validation of 64Cu-ATSM damaging DNA via high-LET Auger electron emission.

Radioactive copper (II) (diacetyl-bis N4-methylthiosemicarbazone) (Cu-ATSM) isotopes were originally developed for the imaging of hypoxia in tumors. Because the decay of a 64Cu atom is emitting not only positrons but also Auger electrons, this radionuclide has great potential as a theranostic agent. However, the success of 64Cu-ATSM internal radiation therapy would depend on the contribution of Auger electrons to tumor cell killing. Therefore, we designed a cell culture system to define the contributions to cell death from Auger electrons to support or refute our hypothesis that the majority of cell death from 64Cu-ATSM is a result of high-LET Auger electrons and not positrons or other low-LET radiation. Chinese hamster ovary (CHO) wild type and DNA repair–deficient xrs5 cells were exposed to 64Cu-ATSM during hypoxic conditions. Surviving fractions were compared with those surviving gamma-radiation, low-LET hadron radiation, and high-LET heavy ion exposure. The ratio of the D10 values (doses required to achieve 10% cell survival) between CHO wild type and xrs5 cells suggested that 64Cu-ATSM toxicity is similar to that of high-LET Carbon ion radiation (70 keV/μm). γH2AX foci assays confirmed DNA double-strand breaks and cluster damage by high-LET Auger electrons from 64Cu decay, and complex types of chromosomal aberrations typical of high-LET radiation were observed after 64Cu-ATSM exposure. The majority of cell death was caused by high-LET radiation. This work provides strong evidence that 64Cu-ATSM damages DNA via high-LET Auger electrons, supporting further study and consideration of 64Cu-ATSM as a cancer treatment modality for hypoxic tumors.

Effect of 17-allylamino-17-demethoxygeldanamycin on radiosensitivity of human lung cancer cell line

Objective To study the radiosensitizing effect of 17-allylamino-17- demethoxygeldana -mycin(17-AAG)on human non-small cell lung cancer cell line(A549 cells), and to investigate its possible mechanism. Methods The growth inhibition effect of 17-AAG on A549 cells was determined using the MTT assay. The radiosensitizing effect of the drug on cells was analyzed using the multi-target single-hit model fitting the colony survival curve. The impacts of the drug on cell aging and DNA damage repair were evaluated using β-galactosidase staining and 7-H2AX immunofluorescence, respectively. Between-group comparison was performed by paired t test or analysis of variance. Results The suppression of cell proliferation by 17-AAG was both dose-dependent and time-dependent(P = 0. 01-0. 05). The radiation group treated with the drug had a lower colony forming efficiency than the radiation-only group. When 50 nmol/L 17-AAG was applied, the radiosensitivity enhancement ratios were 1. 79(the ratio of D0 values)and 2. 30(the ratio of Dq values), respectively. The percentage of senescent cells at 72 hours after exposure was significantly higher in cells exposed to the drug and radiation of 4 Gy X-ray than in the drug-only group(30.48% vs. 9. 18%, P= 0.00)or in the radiation-only group(30.48% vs. 12.30%, P= 0. 00). Immunofluorescent staining showed that 17 - AAG delayed the DNA damage repair. Conclusions 17-AAG has growth inhibition and radiosensitizing effects on human lung cancer A549 cells. Induction of cell aging and delay of DNA damage repair may be involved in the radiosensitizing mechanism. Key words: 17-allylam ino-17-demethoxygeldanamycin; Radiosensitizing; Cell senescence; Deoxyribonucleic acid damage