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Understanding the mechanisms of X-ray radiation damage in biological systems is of prime interest in medicine (radioprotection, X-ray therapy...). Study of low-energy rays, such as soft-X rays and light ions, points to attribute their lethal effect to clusters of energy deposition by low-energy electrons. The first step, at the atomic or molecular level, is often the ionization of inner-shell electrons followed by Auger decay in an aqueous environment. We have developed an experimental set-up to perform electron coincidence spectroscopy on molecules in a water micro-jet. We present here the first results obtained on sodium benzoate solutions, irradiated at the oxygen and carbon K-edges. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-36α, IL-36β and IL-36γ are expressed highly in skin and are involved in the pathogenesis of psoriasis, while the antagonists IL-36Ra or IL-38, another potential IL-36 inhibitor, limit uncontrolled inflammation. The expression and role of IL-36 cytokines in rheumatoid arthritis (RA) and Crohn's disease (CD) is currently debated. Here, we observed that during imiquimod-induced mouse skin inflammation and in human psoriasis, expression of IL-36α, γ and IL-36Ra, but not IL-36β and IL-38 mRNA, was induced and correlated with IL-1β and T helper type 17 (Th17) cytokines (IL-17A, IL-22, IL-23, CCL20). In mice with collagen-induced arthritis and in the synovium of patients with RA, IL-36α, β, γ, IL-36Ra and IL-38 were all elevated and correlated with IL-1β, CCL3, CCL4 and macrophage colony-stimulating factor (M-CSF), but not with Th17 cytokines. In the colon of mice with dextran sulphate sodium-induced colitis and in patients with CD, only IL-36α, γ and IL-38 were induced at relatively low levels and correlated with IL-1β and IL-17A. We suggest that only a minor subgroup of patients with RA (17-29%) or CD (25%) had an elevated IL-36 agonists/antagonists ratio, versus 93% of patients with psoriasis. By immunohistochemistry, IL-36 cytokines were produced by various cell types in skin, synovium and colonic mucosa such as keratinocytes, CD68+ macrophages, dendritic/Langerhans cells and CD79α+ plasma cells. In primary cultures of monocytes or inflammatory macrophages (M1), IL-36β and IL-36Ra were produced constitutively, but IL-36α, γ and IL-38 were produced after lipopolysaccharide stimulation. These distinct expression profiles may help to explain why only subgroups of RA and CD patients have a potentially elevated IL-36 agonists/antagonists ratio. [ABSTRACT FROM AUTHOR]

Modeling proton-induced damage in biological systems, in particular in DNA building blocks, is of major concern in studies on cancer proton therapy. This is indeed an extremely complex process and analysis of the mechanism at the molecular level is of crucial interest. Such collision reactions of protons on biological targets induce different reactions: excitation and ionization of the biomolecule, fragmentation of the ionized species, and charge transfer from the projectile ion toward the biomolecular target. In order to have an insight into such mechanisms, we have performed a theoretical approach of two of the most important steps, the fragmentation and the charge transfer processes. For that purpose, we have considered collision of protons with isolated 2-deoxy-D-ribose by means of ab-initio molecular dynamics and quantum chemistry molecular methods. The conformation of the sugar moiety has been analyzed and appears to induce important effects, in particular different fragmentation patterns have been pointed out with regard to the conformation, and significant variations of the charge transfer cross sections have been exhibited. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Purpose: To study the effect of hydration level and plasmid packing on strand break induction in DNA by ultrasoft X-ray. Materials and methods: Bluescript (pBS, tight packing) and pSP189 (pSP, loose packing) plasmids were irradiated by 250, 380, and 760 eV ultrasoft X-rays at the Laboratoire pour l'Utilisation du Rayonnement Electromagnétique synchrotron facility (Orsay, France). Single and double strand breaks (SSB and DSB) were quantified by gel electrophoresis. Results: The number of DSB per Gray and per Dalton in pBS plasmids were (5.6 ± 0.1), (6.3 ± 0.1) and (8.5 ± 0.4)×10-12 at 250, 380 and 760 eV, respectively. They were respectively 1.4 ± 0.1, 1.1 ± 0.1 and 1.9 ± 0.2 times larger for pSP plasmids. SSB/DSB ratios varied between 4.4 and 6.4. Conclusion: The observed dependency of strand break induction by ultrasoft X-rays on the hydration level of DNA in plasmids films may be associated with: (i) Damage transfer from the water shell to the DNA and/or (ii) change in packing. 760 eV photons which are more often absorbed in the hydration shell and yield longer range electrons than 250 and 380 eV photons, induce more DSB per Gray and per Dalton, especially for the looser plasmid (pSP). [ABSTRACT FROM AUTHOR]

Purpose : To study the frequency of chromosome aberrations induced by soft X-rays. To see if the core ionization of DNA atoms is involved in this end-point as much as it appears to be in cell killing. Materials and methods : V79 hamster cells were irradiated by synchrotron radiation photons iso-attenuated in the cell (250, 350, 810 eV). The morphological chromosome aberrations detected in the first post-irradiation cell division (dicentrics and centric rings) were studied by Giemsa staining. Results : The chromosome aberrations at 350 eV were, respectively, 2.6±0.8 and 2.1±0.8 times more numerous than at 250 and 810 eV for the same average dose absorbed by the nucleus. These relative effectivenesses are comparable with the ones already measured for cell killing. Moreover, they roughly vary such as the relative numbers of core ionizations (including in the phosphorus L-shell) produced in DNA and its bound water (water being involved only at 810 eV through the oxygen atoms). In particular, they reproduce the characteristic twofold enhancement at 350 eV, above the carbon K threshold. Conclusions : Correlations suggest that the core ionization process is likely a common and essential mechanism initiating both chromosome aberration and cell killing end-points at these photon energies. [ABSTRACT FROM AUTHOR]

Abstract: Theoretical simulations are particularly well suited to investigate, at a molecular level, direct and indirect effects of ionising radiations in DNA, as in the particular case of irradiation by swift heavy ions such as those used in hadron therapy. In the past recent years, we have developed the modeling at the microscopic level of the early stages of the Coulomb explosion of DNA molecules immersed in liquid water that follows the irradiation by swift heavy ions. To that end, Time-Dependent Density Functional Theory molecular dynamics simulations (TD-DFT MD) have been developed where localised Wannier orbitals are propagated. This latter enables to separate molecular orbitals of each water molecule from the molecular orbitals of the biomolecule. Our main objective is to demonstrate that the double ionisation of one molecule of the liquid sample, either one water molecule from the solvent or the biomolecule, may be in some cases responsible for the formation of an atomic oxygen as a direct consequence of the molecule Coulomb explosion. Our hypothesis is that the molecular double ionisation arising from irradiation by swift heavy ions (about 10% of ionisation events by ions whose velocity is about the third of speed of light), as a primary event, though maybe less probable than other events resulting from the electronic cascading (for instance, electronic excitations, electron attachments), may be systematically more damageable (and more lethal), as supported by experiments that have been carried out in our group in the 1990s (in studies of damages created by K holes in DNA). The chemical reactivity of the produced atomic oxygen with other radicals present in the medium will ultimately lead to chemical products that are harmful to DNA. In the present paper, we review our theoretical methodology in an attempt that the community be familiar with our new approach. Results on the production of atomic oxygen as a result of the double ionisation of water or as a result of the double ionisation of the Uracil RNA base will be presented. [Copyright &y& Elsevier]