Effect of multiple ionization on the radiolysis of liquid water irradiated with heavy ions a theoretical study using Monte-Carlo simulations

L'eau est un constituant majeur de la plupart des organismes vivants. Elle joue, à ce titre, un rôle central en radiobiologie, en introduisant une part d'effet indirect et/ou quasi direct résultant de sa radiolyse. Une large majorité d'études de chimie sous rayonnement des solutions aqueuses concernent les rayonnements à faible transfert d'énergie linéique (TEL) tels que les rayons y de 6°Co ou les électrons accélérés. Bien qu'elle soit encore incomplète à certains points de vue, un panorama de la radiolyse de l'eau pure ou contenant divers solutés à faible TEL peut être obtenu dans la plupart des cas. Il n'en est cependant pas ainsi pour les rayonnements à grand TEL où plusieurs aspects de cette radiolyse n'ont pas jusqu'ici été pleinement résolus. Parmi les points d'interrogation qui demeurent, citons : (1) le rendement primaire des radicaux hydroperoxyle/anion superoxyde (pKa = 4,8) augmente en fonction du TEL, et ceci même en l'absence d'oxygène. Un tel comportement est contraire à ce que l'on observe pour les autres rendements radicalaires. L'origine de ces radicaux n'est pas clairement établie, même s'ils constituent l'espèce radicalaire principale à haut TEL; (2) le rendement primaire en H20 2 croît avec le TEL jusqu'à un maximum, après lequel il décroît; aucune explication satisfaisante n'a été offerte quant à la présence d'une telle décroissance de ce produit moléculaire à haut TEL; (3) les détails précis du mécanisme par lequel les rayonnements à grand TEL sont très efficaces pour inactiver les cellules tumorales hypoxiques sont encore mal connus. Une interprétation possible de la réduction du facteur d'amplification de l'oxygène (FAO) à haut TEL est donnée par la génération in situ d'un microenvironnement oxygéné autour des trajectoires à grande densité d'ionisation (hypothèse de l'"oxygène à l'intérieur même des trajectoires").Abstract: Water makes up a predominant part of the milieu of living tissue, and, not surprisingly, plays a central role for understanding the interaction of ionizing radiation with biological systems. Most aqueous radiation chemistry studies have involved low-linear energy transfer (LET) radiation, such as [superscript 60]Co [gamma]-rays or fast electrons. A survey of the literature shows that the radiolysis of liquid water at low LET is generally well understood. However, at high LET, several reported data have not hitherto been quantitatively explained : (1) The primary yield of hydroperoxyl/superoxide anion (HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-], p[kappa][subscript a] = 4.8) radicals increases with increasing LET, a behavior that is contrary to the other radical yields. As yet, the origin of these HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] radicals is not clearly established, even though they are the major radical species produced at high LET; (2) The primary yield of hydrogen peroxide rises with increasing LET to a maximum, after which it falls. No suitable explanation for the presence of such a decrease in H[subscript 2]O[subscript 2] yields at high LET has been offered; (3) The exact details of the mechanism by which high-LET radiations are very efficient for the inactivation of tumoral hypoxic cells, are still not well known. One possible explanation for the decreased radiobiological oxygen enhancement ratio (OER) at high LET is offered by the generation in situ of an oxygenated microenvironment around the tracks of more densely ionizing radiations (the so-called"oxygen-in-the-track" hypothesis). This work has been originally motivated by the hypothesis proposed by FERRADINI and JAY-GERIN (1998) that multiple ionization (MI) of water would be responsible for the large HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] yield produced in liquid water subject to heavy-ion irradiation. The purpose of this study is to test the validity of this hypothesis. To this aim, Monte Carlo track structure simulations are used to calculate the G-values of the various radiolytic species, including O[subscript 2], generated in the radiolysis of deaerated liquid water by several different types of radiation ([superscript 1]H[superscript +], [superscript 4]He[superscript 2+], [superscript 12]C[superscript 6+], and [superscript 20]Ne[superscript 9+] ions) over a wide range of LET up to [tilde] 900 keV/[micro]m, at neutral pH and in 0.4 M H[subscript 2]SO[subscript 4] (pH 0.46) solutions at 25ÀC. It is found that, upon incorporating the mechanisms of double, triple, and quadruple ionizations of water in the calculations, a quantitative agreement between theory and experiment can be obtained. In particular, in neutral (pH 7) solutions, our results reproduce very well the large increase observed in [Special characters omitted.] at high LET. Under the conditions of this study, the mechanisms of triple and quadruple ionizations make only a minor contribution to the yield of HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-]. With the exception of protons, our calculations also simultaneously predict a maximum in [Special characters omitted.] around 100-200 keV/[micro]m in accord with experiment. For each irradiating ion considered, this maximum occurs precisely at the point where [Special characters omitted.] begins to rise sharply, suggesting, in agreement with experiments, that the yields of HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] and H[subscript 2]O[subscript 2] are closely linked. Moreover, the incorporation of MI in our simulations has only little effect on the variation of the computed [Special characters omitted.] and G[subscript ¨OH] values as a function of LET. In the case of acidic solutions irradiated by [superscript 12]C[superscript 6+] and [superscript 20]Ne[superscript 9+] ions, our results also predict a well-defined maximum in the curve of [Special characters omitted.] as a function of LET of [tilde] 1.4 molec./100 eV ([tilde] 45% greater in magnitude than that found in neutral water) around 180-200 keV/[micro]m, in good agreement with experiment. Finally, our simulation results show a steep increase in the initial and primary yields of O[subscript 2] with increasing LET. For example, for 24-MeV [superscript 12]C[superscript 6+] ions (LET [tilde] 500 keV/[micro]m), the initial in situ track concentration of oxygen is estimated to be about 3 orders of magnitude higher than the concentration of O[subscript 2] found in typical human cells. Such results, which largely plead in favor of the"oxygen in the heavy-ion track" hypothesis, could have profound consequences in radiobiology and in particular explain the observed reduction in the oxygen enhancement ratio (OER) with increasing LET. In conclusion, our results strongly support the importance of the role of MI in the heavy-ion radiolysis of water at high LET. They suggest that MI, although infrequent relative to single ionization events, is very efficient chemically

Temperature Dependence of the Primary Species Yields of Liquid Water Radiolysis by 0.8-MeV Fast Neutrons

The yields of species such as e-aq, H•, •OH, H2 and H2O2, formed from the radiolysis of neutral liquid water by the incidence of 0.8-MeV neutrons at temperatures between 25 and 350°C, were calculated by using Monte Carlo simulations. The slowing down of these neutrons through elastic scattering produced recoil protons elastically of ~0.5057, 0.186, and 0.0684 MeV which had linear energy transfers (LETs) of ~40, 67 and 76 keV/µm, respectively, at 25°C. The effects of neutron radiation can be predicted based on the contribution of those first three recoil protons by neglecting the radiation effects due to oxygen ion recoils. Then, the fast neutron yields could be estimated by summing the yields of contributing protons after corresponding weightings were used according to their energy. In this work, yields were calculated at 10-7 and 10-6 s after incidence of neutron radiation in water at the aforementioned temperature range. Overall, there is a reasonably good agreement between our calculated and existing experimental G-values for the entire temperature range. However, we proposed an hypothesis that the not very significant difference between experimental data and our calculated data is due to the different measuring time used in obtaining the experimental data as compared to the ones used in our calculation. Our computed yields for 0.8-MeV fast neutron radiation show an essentially similar temperature dependences over the range of temperature studied with 2-MeV fast neutron and low-LET radiation, but with lower values for yields of free radicals and higher values for molecular yields.Received: 04 October 2014; Revised: 23 March 2016; Accepted: 23 March 201

On the Temperature Dependence of the Rate Constant of the Bimolecular Reaction of Two Hydrated Electrons

It has been a longstanding issue in the radiation chemistry of water that, even though H2 is a molecular product, its “escape” yield g(H2) increases with increasing temperature. A main source of H2 is the bimolecular reaction of two hydrated electrons (e-aq). The temperature dependence of the rate constant of this reaction (k1), measured under alkaline conditions, reveals that the rate constant drops abruptly above ~150°C. Recently, it has been suggested that this temperature dependence should be regarded as being independent of pH and used in high-temperature modeling of near-neutral water radiolysis. However, when this drop in the e-aq self-reaction rate constant is included in low (isolated spurs) and high (cylindrical tracks) linear energy transfer (LET) modeling calculations, g(H2) shows a marked downward discontinuity at ~150°C which is not observed experimentally. The consequences of the presence of this discontinuity in g(H2) for both low and high LET radiation are briefly discussed in this communication. It is concluded that the applicability of the sudden drop in k1 observed at ~150°C in alkaline water to near-neutral water is questionable and that further measurements of the rate constant in pure water are highly desirable.Received:13 June 2013; Revised: 27 August 2013; Accepted: 28 August 201

X-irradiation of cells on glass slides has a dose doubling impact

Immunofluorescence detection of γH2AX foci is a widely used tool to quantify the induction and repair of DNA double-strand breaks (DSBs) induced by ionising radiation. We observed that X-irradiation of mammalian cells exposed on glass slides induced twofold higher foci numbers compared to irradiation with γ-rays. Here, we show that the excess γH2AX foci after X-irradiation are produced from secondary radiation particles generated from the irradiation of glass slides. Both 120 kV X-rays and 137Cs γ-rays induce ∼20 γH2AX foci per Gy in cells growing on thin (∼2 μm) plastic foils immersed in water. The same yield is obtained following γ-irradiation of cells growing on glass slides. However, 120 kV X-rays produce ∼40 γH2AX foci per Gy in cells growing on glass, twofold greater than obtained using cells irradiated on plastic surfaces. The same increase in γH2AX foci number is obtained if the plastic foil on which the cells are grown is irradiated on a glass slide. Thus, the physical proximity to the glass material and not morphological differences of cells growing on different surfaces accounts for the excess γH2AX foci. The increase in foci number depends on the energy and is considerably smaller for 25 kV relative to 120 kV X-rays, a finding which can be explained by known physical properties of radiation. The kinetics for the loss of foci, which is taken to represent the rate of DSB repair, as well as the Artemis dependent repair fraction, was similar following X- or γ-irradiation, demonstrating that DSBs induced by this range of treatments are repaired in an identical manner

A highly effective and self-transmissible CRISPR antimicrobial for elimination of target plasmids without antibiotic selection

The use of CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated protein) for sequence-specific elimination of bacteria or resistance genes is a powerful tool for combating antibiotic resistance. However, this approach requires efficient delivery of CRISPR/Cas DNA cassette(s) into the targeted bacterial population. Compared to phage transduction, plasmid conjugation can deliver DNA to a broader host range but often suffers from low delivery efficiency. Here, we developed multi-plasmid conjugation systems for efficient CRISPR/Cas delivery, target DNA elimination and plasmid replacement. The CRISPR/Cas system, delivered via a broad-host-range R1162 mobilizable plasmid, specifically eliminated the targeted plasmid in recipient cells. A self-transmissible RK2 helper plasmid facilitated the spread of mobilizable CRISPR/Cas. The replacement of the target plasmid with another plasmid from the same compatibility group helped speed up target plasmid elimination especially when the target plasmid was also mobilizable. Together, we showed that up to 100% of target plasmid from the entire recipient population could be replaced even at a low (1:180) donor-to-recipient ratio and in the absence of transconjugant selection. Such an ability to modify genetic content of microbiota efficiently in the absence of selection will be critical for future development of CRISPR antimicrobials as well as genetic tools for in situ microbiome engineering

LOW-LINEAR ENERGY TRANSFER RADIOLYSIS OF SUPERCRITICAL WATER AT 400 °C: DENSITY DEPENDENCE OF THE G(•OH)

Monte Carlo simulations were used to predict the yield of primary specie •OH denoted as g(•OH) that is formed from the radiolysis of pure, deaerat- ed supercritical water (SCW) (H2O) at 400 °C in the range of water density between ~0.15 and 0.6 g/ cm3. It is known that •OH, is one of the oxidizing species that significantly can increase the possibil- ity of various corrosion and material degradation as well. The thorough radiolysis processes in SCW- cooled reactor is not established currently, and it is believed to be a challenge in developing chemis- try control strategies for future Supercritical Water Reactor (SCWR). Since SCWR technology is now still under the conceptual design, hence there is only limited information published on the yields of radiolysis under these conditions. In this work, g(•OH) was calculated at spur lifetime (τs/ minimum time needed before the species within spur distributed homogeneously into the bulk solu- tion), 10-7 and 10-6 sec after the ionization event at all densities. From this work, it is shown that the data measured by other researcher at lower density (0.35 g/cm3) is taken about near the spur lifetime. Finally, more experimental data are highly required in order to examine more thoroughly modeling calculation.

Effect of multiple ionization on the radiolysis of liquid water irradiated with heavy ions a theoretical study using Monte-Carlo simulations

Water makes up a predominant part of the milieu of living tissue, and, not surprisingly, plays a central role for understanding the interaction of ionizing radiation with biological systems. Most aqueous radiation chemistry studies have involved low-linear energy transfer (LET) radiation, such as [superscript 60]Co [gamma]-rays or fast electrons. A survey of the literature shows that the radiolysis of liquid water at low LET is generally well understood. However, at high LET, several reported data have not hitherto been quantitatively explained : (1) The primary yield of hydroperoxyl/superoxide anion (HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-], p[kappa][subscript a] = 4.8) radicals increases with increasing LET, a behavior that is contrary to the other radical yields. As yet, the origin of these HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] radicals is not clearly established, even though they are the major radical species produced at high LET; (2) The primary yield of hydrogen peroxide rises with increasing LET to a maximum, after which it falls. No suitable explanation for the presence of such a decrease in H[subscript 2]O[subscript 2] yields at high LET has been offered; (3) The exact details of the mechanism by which high-LET radiations are very efficient for the inactivation of tumoral hypoxic cells, are still not well known. One possible explanation for the decreased radiobiological oxygen enhancement ratio (OER) at high LET is offered by the generation in situ of an oxygenated microenvironment around the tracks of more densely ionizing radiations (the so-called"oxygen-in-the-track" hypothesis). This work has been originally motivated by the hypothesis proposed by FERRADINI and JAY-GERIN (1998) that multiple ionization (MI) of water would be responsible for the large HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] yield produced in liquid water subject to heavy-ion irradiation. The purpose of this study is to test the validity of this hypothesis. To this aim, Monte Carlo track structure simulations are used to calculate the G-values of the various radiolytic species, including O[subscript 2], generated in the radiolysis of deaerated liquid water by several different types of radiation ([superscript 1]H[superscript +], [superscript 4]He[superscript 2+], [superscript 12]C[superscript 6+], and [superscript 20]Ne[superscript 9+] ions) over a wide range of LET up to [tilde] 900 keV/[micro]m, at neutral pH and in 0.4 M H[subscript 2]SO[subscript 4] (pH 0.46) solutions at 25ÀC. It is found that, upon incorporating the mechanisms of double, triple, and quadruple ionizations of water in the calculations, a quantitative agreement between theory and experiment can be obtained. In particular, in neutral (pH 7) solutions, our results reproduce very well the large increase observed in [Special characters omitted.] at high LET. Under the conditions of this study, the mechanisms of triple and quadruple ionizations make only a minor contribution to the yield of HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-]. With the exception of protons, our calculations also simultaneously predict a maximum in [Special characters omitted.] around 100-200 keV/[micro]m in accord with experiment. For each irradiating ion considered, this maximum occurs precisely at the point where [Special characters omitted.] begins to rise sharply, suggesting, in agreement with experiments, that the yields of HO[subscript 2][superscript ¨]/O[subscript 2][superscript ¨-] and H[subscript 2]O[subscript 2] are closely linked. Moreover, the incorporation of MI in our simulations has only little effect on the variation of the computed [Special characters omitted.] and G[subscript ¨OH] values as a function of LET. In the case of acidic solutions irradiated by [superscript 12]C[superscript 6+] and [superscript 20]Ne[superscript 9+] ions, our results also predict a well-defined maximum in the curve of [Special characters omitted.] as a function of LET of [tilde] 1.4 molec./100 eV ([tilde] 45% greater in magnitude than that found in neutral water) around 180-200 keV/[micro]m, in good agreement with experiment. Finally, our simulation results show a steep increase in the initial and primary yields of O[subscript 2] with increasing LET. For example, for 24-MeV [superscript 12]C[superscript 6+] ions (LET [tilde] 500 keV/[micro]m), the initial in situ track concentration of oxygen is estimated to be about 3 orders of magnitude higher than the concentration of O[subscript 2] found in typical human cells. Such results, which largely plead in favor of the"oxygen in the heavy-ion track" hypothesis, could have profound consequences in radiobiology and in particular explain the observed reduction in the oxygen enhancement ratio (OER) with increasing LET. In conclusion, our results strongly support the importance of the role of MI in the heavy-ion radiolysis of water at high LET. They suggest that MI, although infrequent relative to single ionization events, is very efficient chemically

High-dose-rate effects in the radiolysis of water at elevated temperatures.

Monte Carlo track chemistry simulations were used to study the effects of high dose rates on the radical (e-aq, H•, and •OH) and molecular (H2 and H2O2) yields in the low linear energy transfer (LET) radiolysis of liquid water at elevated temperatures between 25–350 C. Our simulation model consisted of randomly irradiating water by single pulses of N incident protons of 300 MeV (LET ~ 0.3 keV/μm), which penetrate at the same time perpendicular to this water within the surface of a circle. The effect of dose rate was studied by varying N. Our simulations showed that, at any given temperature, the radical products decrease with increasing dose rate and, at the same time, the molecular products increase, resulting from an increase in the inter-track, radical-radical reactions. Using the kinetics of the decay of hydrated electrons at 25 and 350 C, we determined a critical time (τc) for each value of N, which corresponds to the “onset” of dose-rate effects. For our irradiation model, τc was inversely proportional to N for the two temperatures considered, with τc at 350 C being shifted by an order of magnitude to shorter times compared to its values at 25 C. Finally, the data obtained from the simulations for N = 2,000 generally agreed with the observation that during the track stage of the radiolysis, free radical yields increase, while molecular products decrease with increasing temperature from 25 to 350 C. The exceptions of e-aq and H2 to this general pattern are briefly discussed.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author