Radiation-induced Modifications Research Articles

Aspects of γ-radiation induced modification of calf thymus DNA in the presence of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulfonate and its transition metal complexes with Cu2+ and Ni2+

Radiation-induced double-strand modification of DNA was studied in the absence and presence of sodium 1,4-dihydroxy-9,10-anthraquinone-2-sulfonate (NaQSH2) and its metal (Cu2+ and Ni2+) complexes in aerated, de-aerated (Argon saturated) and N2O saturated aqueous media at pH 7.4. Ethidium bromide, an established DNA intercalator was used to estimate DNA remaining after interaction with γ-radiation, by measuring loss of fluorescence of the ethidium bromide–DNA adduct. In de-aerated (Argon saturated) and N2O saturated aqueous media radiation-induced double-strand modification of calf thymus DNA was comparatively less in presence of NaQSH2 and its Ni(II) complex than standard control indicating the compounds behaved as radio-protectors. However, in presence of the Cu(II) complex radiation-induced double-strand modification increased significantly. In N2O saturated medium, double-strand modification of DNA was almost double in all cases than that observed in de-aerated (Argon saturated) medium indicating OH radicals played a major role in modifying DNA. That OH radicals were important was verified by repeating experiments using tertiary-butanol that showed significant decrease in DNA modification. Another important observation was in aerated medium NaQSH2, Ni(II)–NaQSH2 did not show radioprotection while Cu(II)–NaQSH2 was an almost equally effective radiosensitizer as that observed in N2O saturated medium. Role of molecular oxygen as radiosensitizer was thus realized.

Thermoluminescence in gamma irradiated iPP-VGVGCNF

Nanocomposites have been obtained by dispersing various amounts of vapor grown carbon nanofibers within isotactic polypropylene via melt mixing. The as obtained nanocomposites were gamma irradiated at various integral doses by using a 60Co source. The irradiation was performed in air, at room temperature, and at a dose rate of about 1kGy/h up to an integral dose of 28kGy. Thermoluminescence investigations revealed the role of carbon nanotubes in the radiation-induced modification of polymer-based nanocomposites. Almost all samples (pristine polymer and polymer-based nanocomposites irradiated and not irradiated) showed two overlapping thermoluminescence signals. It is concluded that the dispersion of carbon nanotubes decreases the amount of trapped electrons improving eventually the radiation stability of the polymeric matrix. The low temperature thermoluminescence peak was tentatively associated to melting phenomena. The origin of the high temperature thermoluminescence peak is more complex. Nevertheless, the experimental data suggests that this peak is sensitive to the polymer-filler interface.

Ionizing radiation, ion transports, and radioresistance of cancer cells

The standard treatment of many tumor entities comprises fractionated radiation therapy which applies ionizing radiation to the tumor-bearing target volume. Ionizing radiation causes double-strand breaks in the DNA backbone that result in cell death if the number of DNA double-strand breaks exceeds the DNA repair capacity of the tumor cell. Ionizing radiation reportedly does not only act on the DNA in the nucleus but also on the plasma membrane. In particular, ionizing radiation-induced modifications of ion channels and transporters have been reported. Importantly, these altered transports seem to contribute to the survival of the irradiated tumor cells. The present review article summarizes our current knowledge on the underlying mechanisms and introduces strategies to radiosensitize tumor cells by targeting plasma membrane ion transports.

Radiation-induced modification of human somatic cells’ chromosome sensitivity to the testing mutagenic exposure of bleomycin in vitro in lung cancer patients in delayed terms following chernobyl accident

By using modified "G2-bleomycin sensitivity assay" above background level of cytogenetic effect considered as a marker of hidden chromosome instability (HCI) has been investigated in 3 groups--liquidators of Chernobyl accident (occupational group 1), patients with lung cancer who denied conscious contact--with ionizing radiation (group of comparison), liquidators with lung cancer (occupational group 2). Significant interindividual variations of cytogenetic effects induced with bleomycin and the lack of positive correlation between background and above background frequencies of chromosome aberrations have been shown in all observed groups. It had been established that occupational group 2 was the most burdened group by expression of the above background cytogenetic effect and, accordingly, number of persons with HCI. The data obtained permit to suggest the existence of the association between radiation-induced increase of individual sensitivity to testing mutagenic exposure and the realization of cancer in persons exposed to ionizing radiation. The results show acceptability of "G2-bleomycin sensitivity assay" under the cytogenetic examination of irradiated contingents for determining HCI as one of informative markers of predisposition to oncopathology.

Evaluation of “Payne effect” in radiation-induced modification of chlorobutyl rubber

The major effect of high energy photon, such as gamma rays, in organic polymers is the generation of free radicals, causing changes in electrical, optical and mechanical properties. This work aims to the study of a controlled degradation of a chlorobutyl rubber compound after irradiation at: 25, 100 and 200kGy doses. Effects of irradiation on a rubber compound were investigated via DMA (Dynamic Mechanical Analysis) tests using the so-called Payne effect, which is directly related to the dynamic properties of the vulcanized rubber. The test begins in a low strain excitation upwards to a maximum programmed strain, and then downwards to a minimum strain at room temperature. The dependency of the material related to the strain amplitude is illustrated by Payne effect. Material behavior presents a non linear evolution on both modulus and Tan when increasing the strain (Payne effect). A difference on G′ and tangent δ values at low strain can be observed between the sweeping ways up and down. The difference between new and irradiated material at 25kGy dose material is not very significant. Nevertheless, the chain scission for higher irradiation doses (≥25kGy) is verified, as observed by Payne effect. Another interest in strain sweep is to facilitate the detection of strong breaking in materials linkage at high strain amplitude as illustrated by Mullins effect.

Improvement of human skin cell growth by radiation-induced modifications of a Ge/Ch/Ha scaffold

Gelatin-/chitosan-/hyaluronan-based biomaterials are used in tissue engineering as cell scaffolds. Three gamma radiation doses (1, 10 and 25kGy) were applied to scaffolds for sterilization. Microstructural changes of the irradiated polymers were evaluated by using scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). A dose of 25kGy produced a rough microstructure with a reduction of the porosity (from 99 to 96%) and pore size (from 160 to 123μm). Radiation also modified the glass transition temperature between 31.2 and 42.1°C (1 and 25kGy respectively). Human skin cells cultivated on scaffolds irradiated with 10 and 25kGy proliferated at 48h and secreted transforming growth factor β3 (TGF-β3). Doses of 0kGy (non-irradiated) or 1kGy did not stimulate TGF-β3 secretion or cell proliferation. The specific growth rate and lactate production increased proportionally to radiation dose. The use of an appropriate radiation dose improves the cell scaffold properties of biomaterials.

Density variation of parotid glands during IMRT for head–neck cancer: Correlation with treatment and anatomical parameters

PurposeMeasuring parotid density changes in patients treated with IMRT for head–neck cancer (HNC) and assessing correlation with treatment-related parameters. Patients and materialsData of 84 patients treated with IMRT for different HNC were pooled from three institutions. Parotid deformation and average Hounsfield number changes (ΔHU) were evaluated through MVCT (with Helical Tomotherapy) or diagnostic kVCT images taken at the treatment start/end. Parotids were delineated in the first image and propagated to the last using a previously validated algorithm based on elastic registration. The correlation between ΔHU and several treatment-related parameters was tested; then, logistic uni- and multi-variate analyses taking “large” ΔHU as end-point were carried out. Due to the better image quality, analyses were repeated considering only kVCT data. ResultsΔHU was negative in 116/168 parotids (69%; for kVCT patients: 72/92, 78%). The average ΔHU was significantly different from zero (−7.3, 0.20–0.25HU/fraction, p<0.001). Individual ΔHU was highly correlated with parotid deformation both in terms of volume change and mean value of the Jacobian of the deformation field (Jac_mean), and with neck thickness variation; these correlations were much stronger for kVCT data. Logistic analyses considering ΔHU<−11 (quartile value) as the end-point showed a two-variable model including large deformation (Jac_mean<0.68) and initial neck thickness to be the most predictive variables (p<0.0005, AUC=0.683; AUC=0.776 for kVCT); the odd ratio of large vs moderate/small parotid deformation was 3.8 and 8.0 for the whole and the kVCT population respectively. ConclusionsParotid density reduced in most patients during IMRT and this phenomenon was highly correlated with parotid deformation. The individual assessment of density changes was highly reliable just with diagnostic KvCT. Density changes should be considered as an additional objective measurement of early parotid radiation-induced modifications; further research is warranted.

Radiation-induced modification of titanium nickelide with fast neutrons

We present a review of the investigations of the effect of fast neutrons on the structure and properties of titanium nickelide that were performed by the authors on an IVV-2M atomic reactor (Zarechnyi). It has been established that at small fluences of fast neutrons atomic disordering of crystals is observed; as the fluence increases, the material becomes partially amorphized; and at fluences higher than 1 × 1020 cm−2, the material transforms completely into the amorphous state. It has been shown that the amorphous state produced by neutron irradiation differs substantially from the amorphous state of materials obtained by conventional methods. In particular, if a single-crystal specimen is subjected to “neutron” amorphization (most of the investigations were carried out using single crystals), after annealing of radiation-induced defects the single crystal is restored with the initial orientation and perfection. The structural studies were conducted by the methods of neutron and X-ray diffraction. Based on these studies, as well as on the results of small-angle neutron scattering and dilatometric and resistivity measurements, the “defect” state of irradiated materials has been examined in detail. The radiation resistance of titanium nickelide has been estimated.

The TGF-β/Smad Repressor TG-Interacting Factor 1 (TGIF1) Plays a Role in Radiation-Induced Intestinal Injury Independently of a Smad Signaling Pathway

Despite advances in radiation delivery protocols, exposure of normal tissues during the course of radiation therapy remains a limiting factor of cancer treatment. If the canonical TGF-β/Smad pathway has been extensively studied and implicated in the development of radiation damage in various organs, the precise modalities of its activation following radiation exposure remain elusive. In the present study, we hypothesized that TGF-β1 signaling and target genes expression may depend on radiation-induced modifications in Smad transcriptional co-repressors/inhibitors expressions (TGIF1, SnoN, Ski and Smad7). In endothelial cells (HUVECs) and in a model of experimental radiation enteropathy in mice, radiation exposure increases expression of TGF-β/Smad pathway and of its target gene PAI-1, together with the overexpression of Smad co-repressor TGIF1. In mice, TGIF1 deficiency is not associated with changes in the expression of radiation-induced TGF-β pathway-related transcripts following localized small intestinal irradiation. In HUVECs, TGIF1 overexpression or silencing has no influence either on the radiation-induced Smad activation or the Smad3-dependent PAI-1 overexpression. However, TGIF1 genetic deficiency sensitizes mice to radiation-induced intestinal damage after total body or localized small intestinal radiation exposure, demonstrating that TGIF1 plays a role in radiation-induced intestinal injury. In conclusion, the TGF-β/Smad co-repressor TGIF1 plays a role in radiation-induced normal tissue damage by a Smad-independent mechanism.

Reply to Röglin et al.: Synchrotron radiation-induced covalent modification of 14-3-3ζ by diazene compounds containing pyridoxal phosphate

In the letter by Roglin et al. (1), the authors show that pyridoxal phosphate (PLP) derivatives form reversible covalent imine adducts with lysine(s) of 14-3-3σ through coupling between the N6-amine group of lysine and the aldehyde group of the compound. Their X-ray diffraction experiments are performed by using Cu-Kα radiation with a wavelength of 1.5418 A and the crystals obtained under crystallization conditions with pH 7.4. In our original study (2), we discussed the imine adduct model for 14-3-3ζ protein interactions with FOBISIN101, a small molecule containing an -N=N- diazene bond that links the pyridoxal phosphate and benzoate moieties. However, under our experimental conditions (pH 8.5 and synchrotron radiation of 1.0 A wavelength), we observed radical-mediated hydrazine adduct formation (as supported by the evidence detailed later). Notably, the described imine formation (1) is more likely to occur at pH 7.4 relative to pH 8.5.

Kinetics of electron-beam dispersion of fullerite C60

Electron-beam dispersion of pressed fullerite C60 targets in vacuum leads to the deposition of thin films containing polymeric forms of C60. The aim of the present report is to analyze physical–chemical processes in the fullerite target during its electron-beam dispersion through the analysis of the kinetics of the radiation temperature of the target surface, the coating growth rate and the density of negative current on the substrate. It was shown that the induction stage of the process is determined by the negative charging and radiation-induced modification and heating of the target. The transitional stage is characterized by nonstationary sublimation of the target material through the pores in the modified surface layer and release of the accumulated negative charge. Stabilization of the process parameters owing to the convection cooling of the target by the sublimation products and the decrease in the pressure inside the microcavities beneath the pores leads to a quasi-stationary stage of target sublimation and deposition of a coating containing polymeric forms of C60.

Recent developments in research on water oxidation by photosystem II

Photosynthetic water oxidation chemistry at the unique manganese-calcium complex of photosystem II (PSII) is of fundamental importance and serves as a paragon in the development of efficient synthetic catalysts. A recent crystal structure of PSII shows the atoms of the water-oxidizing complex; its Mn4CaO5 core resembles inorganic manganese-calcium oxides. Merging of crystallographic and spectroscopic information reverses radiation-induced modifications at the Mn-complex in silico and facilitates discussion of the O-O bond chemistry. Coordinated proton movements are promoted by a water network connecting the Mn4CaO5 core with the oxidant, a tyrosine radical and one possibly mobile chloride ion. A basic reaction-cycle model predicts an alternating proton and electron removal from the catalytic site, which facilitates energetically efficient water oxidation.

Complete relaxation map of polypropylene: radiation-induced modification as dielectric probe

The molecular relaxation behaviour of isotactic polypropylene (iPP) exposed to gamma radiation in air to various absorbed doses (up to 700 kGy) has been investigated by dielectric loss (\( { \tan }\;\delta \)) analysis; the polar (mainly carbonyl and hydroperoxide) groups that were introduced by radiation-induced oxidation were considered as tracer groups. All relaxation zones (α, β, γ and δ in the order of decreasing temperature), between 25 K and melting temperature, were studied in the frequency range from 1 kHz to 1 MHz. The changes observed in the dielectric relaxation spectra were related to the modifications in the structural and morphological parameters attributed to exposure of the iPP samples to radiation. Wide-angle X-ray diffraction was used to investigate radiation-induced changes in the crystalline structure and degree of crystallinity, since the α relaxation is connected with this phase. Infrared spectroscopy and gel measurements were used to determine the changes in the oxidative degradation and the degree of network formation, respectively. Conclusions derived using different methods were compared. This study reveals high dielectric and/or relaxation sensitivity of iPP to gamma radiation. Disappearance of the low-temperature dielectric (γ and δ) relaxations together with large changes in intensity, position and activation energy of the dielectric α relaxation are observed with gamma irradiation and are mainly connected with oxidative degradation in iPP structure.

High-valent [MnFe] and [FeFe] cofactors in ribonucleotide reductases

Ribonucleotide reductases (RNRs) are essential for DNA synthesis in most organisms. In class-Ic RNR from Chlamydia trachomatis (Ct), a MnFe cofactor in subunit R2 forms the site required for enzyme activity, instead of an FeFe cofactor plus a redox-active tyrosine in class-Ia RNRs, for example in mouse (Mus musculus, Mm). For R2 proteins from Ct and Mm, either grown in the presence of, or reconstituted with Mn and Fe ions, structural and electronic properties of higher valence MnFe and FeFe sites were determined by X-ray absorption spectroscopy and complementary techniques, in combination with bond-valence-sum and density functional theory calculations. At least ten different cofactor species could be tentatively distinguished. In Ct R2, two different Mn(IV)Fe(III) site configurations were assigned either L4MnIV(μO)2FeIIIL4 (metal–metal distance of ~2.75Å, L = ligand) prevailing in metal-grown R2, or L4MnIV(μO)(μOH)FeIIIL4 (~2.90Å) dominating in metal-reconstituted R2. Specific spectroscopic features were attributed to an Fe(IV)Fe(III) site (~2.55Å) with a L4FeIV(μO)2FeIIIL3 core structure. Several Mn,Fe(III)Fe(III) (~2.9–3.1Å) and Mn,Fe(III)Fe(II) species (~3.3–3.4Å) likely showed 5-coordinated Mn(III) or Fe(III). Rapid X-ray photoreduction of iron and shorter metal–metal distances in the high-valent states suggested radiation-induced modifications in most crystal structures of R2. The actual configuration of the MnFe and FeFe cofactors seems to depend on assembly sequences, bound metal type, valence state, and previous catalytic activity involving subunit R1. In Ct R2, the protonation of a bridging oxide in the MnIV(μO)(μOH)FeIII core may be important for preventing premature site reduction and initiation of the radical chemistry in R1.

Swift heavy ion-induced modification of the physical properties of polymethyl methacrylate/carbon black composites

A carbon black (CB) filler was inserted into polymethyl methacrylate (PMMA) using a chemical route method. The electrical conductivity and dielectric properties of PMMA/CB composites were investigated in a wide range of frequencies: from 100 Hz to 10 MHz. These films were irradiated with 140 MeV Ag11+ ions at a fluence of 1×1012 ions/cm2. The radiation-induced modifications in the dielectric, structural and thermal properties and in the surface morphology were studied using different techniques. The dielectric dispersion and conductivity of the composite system exhibited a strong frequency dependence, particularly in the vicinity of the percolation threshold (20 wt%). It was observed that the dielectric constant, dielectric loss and electrical conductivity gradually increased with the filler concentration and also with ion fluence; these were explained in terms of the hopping conduction mechanism. The electrical conductivity of the composites obeys the universal power law (i.e. σ=Af n ), where n is the power exponent. The results also suggest that ion beam irradiation of polymer composites creates free radicals and unsaturation and causes interfacial polarization in the heterogeneous composite systems. Thermal analysis revealed that the glass transition temperature (T g) shifted toward lower temperatures upon irradiation, indicating the scissioning of polymer chains which led to the transformation of the polymers into a disordered amorphous state. The changes in the topography of the surfaces upon irradiation were also observed.

Radiation-induced modifications of the tumor microenvironment promote metastasis

Radiotherapy is successfully used to treat cancer. Emerging evidence, however, indicates that recurrences after radiotherapy are associated with increased local invasion, metastatic spreading and poor prognosis. Radiation-induced modifications of the tumor microenvironment have been proposed to contribute to increased aggressive tumor behavior, an effect also referred to as tumor bed effect, but the putative mechanisms involved have remained largely elusive. We have recently demonstrated that irradiation of the prospective tumor stroma impairs de novo angiogenesis through sustained inhibition of proliferation, migration and sprouting of endothelial cells. Experimental tumors growing within a pre-irradiated field have reduced tumor angiogenesis and tumor growth, increased hypoxia, necrosis, local invasion and distant metastasis. Mechanisms of progression involve adaptation of tumor cells to local hypoxic conditions as well as selection of cells with invasive and metastatic capacities. The matricellular protein CYR61 and integrin αVβ5 emerged as molecules that cooperate to mediate lung metastasis. Cilengitide, a small molecular inhibitor of αV integrins prevented lung metastasis formation. These results represent a conceptual advance to the understanding of the tumor bed effect and indicate that αV integrin inhibition might be a potential therapeutic approach for preventing metastasis in patients at risk for post-radiation recurrences.

Radiation induced changes in electrical conductivity of chemical vapor deposited silicon carbides under fast neutron and gamma-ray irradiations

The radiation-induced changes in the volume electrical conductivities of chemical vapor deposited silicon carbides (CVD-SiCs) were in-site investigated by performing irradiation using 1.17 and 1.33-MeV gamma-ray and 14-MeV fast neutron beams in air and vacuum. Under gamma-ray irradiation at ionization dose rates of 3.6 and 5.9 Gy/s and irradiation temperature of approximately 300 K, the initial rapid increase in electrical conductivity; this is indicative of radiation-induced conductivity (RIC), occurred due to electronic excitation, and a more gradual increase followed up to a dose of approximately 10–50 kGy corresponding to the results in base conductivity without radiation; this is indicative of radiation-induced electrical degradation (RIED). However, the radiation-induced phenomena were not observed at irradiation temperatures above 373 K. Under neutron irradiation at a further low dose rate below approximately 2.1 Gy/s, a fast neutron flux of 9.2 × 10 14 n/m 2 s, and 300 K, the RIED-like behavior according to radiation-induced modification of the electrical property occurred with essentially no displacement damage, but ionizing effects (radiolysis).

Molecular dynamics simulation of radiation damage in glasses

Molecular dynamics simulations of the ballistic effects arising from displacement cascades in glasses have been investigated in silica and in a SiO 2–B 2O 3–Na 2O glass. In both glasses the T-O-T′ angle (where T and T′ are network formers) diminishes, despite radiation causes opposite effects: while the ternary glass swells and silica becomes denser. We show that radiation-induced modifications of macroscopic glass properties result from structural change at medium/range, reflecting an increasing disorder and internal energy of the system. A local thermal quenching model is proposed to account for the effects of ballistic collisions. The core of a displacement cascade is heated by the passage of the projectile, then rapidly quenched, leading to a process that mimics a local thermal quenching. The observed changes in both the mechanical and structural properties of glasses eventually reach saturation at 2 10 18 α/g as the accumulated energy increases. The passage of a single projectile is sufficient to reach the maximum degree of damage, confirming the hypothesis postulated in the swelling model proposed by J.A.C. Marples.

Radiation-induced reductive modifications of sulfur-containing amino acids within peptides and proteins

The complex scenario of radical stress reactions affecting peptides/proteins can be better elucidated through the design of biomimetic studies simulating the consequences of the different free radicals attacking amino acids. In this context, ionizing radiations allowed to examine the specific damages caused by H-atoms and electrons coupled with protons, thus establishing the molecular basis of reductive radical stress. This is an innovative concept that complements the well-known oxidative stress also in view of a complete understanding of the global consequences of radical species reactivities on living systems. This review summarizes the knowledge of the chemical changes present in sulfur-containing amino acids occurring in polypeptides under reductive radical conditions, in particular the transformation of Met and Cys residues into α-amino butyric acid and alanine, respectively. Reductive radical stress causing a desulfurization process, is therefore coupled with the formation of S-centered radicals, which in turn can diffuse apart and become responsible of the damage transfer from proteins to lipids. These reductive modifications assayed in different peptide/protein sequences constitute an integration of the molecular inventories that up to now take into account only oxidative transformations. They can be useful to achieve an integrated vision of the free radical reactivities in a multifunctional system and, overall, for wider applications in the redox proteomics field.

Human serum albumin modifications associated with reductive radical stress

Radiation-induced modifications of human serum albumin mainly occurring at S-containing residues were investigated by Raman spectroscopy and mass spectrometry techniques. When HO˙ radicals were scavenged by t-BuOH, the H˙ atom and hydrated electron (e(aq)(-)) attack led to the chemical transformation of Cys into Ala residues and the conversion of Met residues into α-aminobutyric acid residues. Mapping experiments demonstrated that desulfurization selectively affects Cys34, Met123, Met298, Cys514, Met548 and Cys567 since the first stages of reaction. Generation of thiol functionality was also detected at specific residues involved in disulfide bonds, namely Cys200, Cys392 and Cys514, together with partial oxidation at Met87, Met123, Met298, Met329 and Met548, forming sulfoxides. When HO˙ radicals were not scavenged, lesser amounts of the previous modifications were observed, whereas some residues (Cys34, Cys461, Pro486, Phe488 and Phe502) resulted to be oxidatively modified. Based on the known cystine pairing in native albumin, no relationships were observed between desulfurization and disulfide reduction processes at Cys residues involved in disulfide bonds, thus suggesting either independent reactivities or, more probably, reactions at the same amino acids that then underwent quick disulfide scrambling events toward more stable disulfide/thiol populations. When these reactions were performed on protein species added to large unilamellar vesicles, desulfurization yielded sulfur radicals able to induce a cis-trans isomerization of lipids at the onset of irradiation. This study provides a description of the human albumin modifications resulting from reductive radical stress, thus suggesting the need for specific assays and future investigations to detect these events in proteins and lipids within challenged cells.