Effets des électrons secondaires sur l'ADN

Les interactions des électrons de basse énergie (EBE) représentent un élément important en sciences des radiations, particulièrement, les séquences se produisant immédiatement après l'interaction de la radiation ionisante avec le milieu biologique. Il est bien connu que lorsque ces radiations déposent leur énergie dans la cellule, elles produisent un grand nombre d'électrons secondaires (4x10[indice supérieur 4]/MeV), qui sont créés le long de la trace avec des énergies cinétiques initiales bien inférieures à 20 eV. Cependant, il n'y a jamais eu de mesures directes démontrant l'interaction de ces électrons de très basse énergie avec l'ADN, dû principalement aux difficultés expérimentales imposées par la complexité du milieu biologique. Dans notre laboratoire, les dernières années ont été consacrées à l'étude des phénomènes fondamentaux induits par impact des EBE sur différentes molécules simples (e.g., N[indice inférieur 2] , CO, O[indice inférieur 2] , H[indice inférieur 2]O, NO, C[indice inférieur 2]H[indice inférieur]4, C[indice inférieur 6]H[indice inférieur 6], C[indice inférieur 2]H[indice inférieur 12]) et quelques molécules complexes dans leur phase solide. D'autres travaux effectués récemment sur des bases de l'ADN et des oligonucléotides ont montré que les EBE produisent des bris moléculaires sur les biomolécules. Ces travaux nous ont permis d'élaborer des techniques pour mettre en évidence et comprendre les interactions fondamentales des EBE avec des molécules d'intérêt biologique, afin d'atteindre notre objectif majeur d'étudier l'effet direct de ces particules sur la molécule d'ADN.Les techniques de sciences des surfaces développées et utilisées dans les études précitées peuvent être étendues et combinées avec des méthodes classiques de biologie pour étudier les dommages de l'ADN induits par l'impact des EBE. Nos expériences ont montré l'efficacité des électrons de 3-20 eV à induire des coupures simple et double brins dans l'ADN. Pour des énergies inférieures à 15 eV, ces coupures sont induites par la localisation temporaire d'un électron sur une unité moléculaire de l'ADN, ce qui engendre la formation d'un ion négatif transitoire dans un état électronique dissociatif, cette localisation est suivie d'une fragmentation. À plus haute énergie, la dissociation dipolaire (i.e., la formation simultanée d'un ion positif et négatif) et l'ionisation jouent un rôle important dans le dommage de l'ADN. L'ensemble de nos résultats permet d'expliquer les mécanismes de dégradation de l'ADN par les EBE et d'obtenir des sections efficaces effectives des différents types de dommages

FERM3D: A finite element R-matrix electron molecule scattering code

FERM3D is a three-dimensional finite element program, for the elastic scattering of a low energy electron from a general polyatomic molecule, which is converted to a potential scattering problem. The code is based on tricubic polynomials in spherical coordinates. The electron-molecule interaction is treated as a sum of three terms: electrostatic, exchange. and polarisation. The electrostatic term can be extracted directly from ab initio codes ({\sc{GAUSSIAN 98}} in the work described here), while the exchange term is approximated using a local density functional. A local polarisation potential based on density functional theory [C. Lee, W. Yang and R. G. Parr, {Phys. Rev. B} {37}, (1988) 785] describes the long range attraction to the molecular target induced by the scattering electron. Photoionisation calculations are also possible and illustrated in the present work. The generality and simplicity of the approach is important in extending electron-scattering calculations to more complex targets than it is possible with other methods.Comment: 30 pages, 4 figures, preprint, Computer Physics Communications (in press

Electron induced chemistry: a new frontier in astrochemistry

The commissioning of the ALMA array and the next generation of space telescopes heralds the dawn of a new age of Astronomy, in which the role of chemistry in the interstellar medium and in star and planet formation may be quantified. A vital part of these studies will be to determine the molecular complexity in these seemingly hostile regions and explore how molecules are synthesised and survive. The current hypothesis is that many of these species are formed within the ice mantles on interstellar dust grains with irradiation by UV light or cosmic rays stimulating chemical reactions. However, such irradiation releases many secondary electrons which may themselves induce chemistry. In this article we discuss the potential role of such electron induced chemistry and demonstrate, through some simple experiments, the rich molecular synthesis that this may lead to

Influence of laser parameters and staining on femtosecond laser-based intracellular nanosurgery

Femtosecond (fs) laser-based intracellular nanosurgery has become an important tool in cell biology, albeit the mechanisms in the so-called low-density plasma regime are largely unknown. Previous calculations of free-electron densities for intracellular surgery used water as a model substance for biological media and neglected the presence of dye and biomolecules. In addition, it is still unclear on which time scales free-electron and free-radical induced chemical effects take place in a cellular environment. Here, we present our experimental study on the influence of laser parameters and staining on the intracellular ablation threshold in the low-density plasma regime. We found that the ablation effect of fs laser pulse trains resulted from the accumulation of single-shot multiphoton-induced photochemical effects finished within a few nanoseconds. At the threshold, the number of applied pulses was inversely proportional to a higher order of the irradiance, depending on the laser repetition rate and wavelength. Furthermore, fluorescence staining of subcellular structures before surgery significantly decreased the ablation threshold. Based on our findings, we propose that dye molecules are the major source for providing seed electrons for the ionization cascade. Consequently, future calculations of free-electron densities for intracellular nanosurgery have to take them into account, especially in the calculations of multiphoton ionization rates

Electron attachment-induced DNA single-strand breaks at the pyrimidine sites

To elucidate the contribution of pyrimidine in DNA strand breaks caused by low-energy electrons (LEEs), theoretical investigations of the LEE attachment-induced C3′–O3′, and C5′–O5′ σ bond as well as N-glycosidic bond breaking of 2′-deoxycytidine-3′,5′-diphosphate and 2′-deoxythymidine-3′,5′-diphosphate were performed using the B3LYP/DZP++ approach. The base-centered radical anions are electronically stable enough to assure that either the C–O or glycosidic bond breaking processes might compete with the electron detachment and yield corresponding radical fragments and anions. In the gas phase, the computed glycosidic bond breaking activation energy (24.1 kcal/mol) excludes the base release pathway. The low-energy barrier for the C3′–O3′ σ bond cleavage process (∼6.0 kcal/mol for both cytidine and thymidine) suggests that this reaction pathway is the most favorable one as compared to other possible pathways. On the other hand, the relatively low activation energy barrier (∼14 kcal/mol) for the C5′–O5′ σ bond cleavage process indicates that this bond breaking pathway could be possible, especially when the incident electrons have relatively high energy (a few electronvolts). The presence of the polarizable medium greatly increases the activation energies of either C–O σ bond cleavage processes or the N-glycosidic bond breaking process. The only possible pathway that dominates the LEE-induced DNA single strands in the presence of the polarizable surroundings (such as in an aqueous solution) is the C3′–O3′ σ bond cleavage (the relatively low activation energy barrier, ∼13.4 kcal/mol, has been predicted through a polarizable continuum model investigation). The qualitative agreement between the ratio for the bond breaks of C5′–O5′, C3′–O3′ and N-glycosidic bonds observed in the experiment of oligonucleotide tetramer CGAT and the theoretical sequence of the bond breaking reaction pathways have been found. This consistency between the theoretical predictions and the experimental observations provides strong supportive evidences for the base-centered radical anion mechanism of the LEE-induced single-strand bond breaking around the pyrimidine sites of the DNA single strands

Radio- and photosensitization of DNA with compounds containing platinum and bromine atoms

Irradiations of plasmid DNA by both X-rays and UV light in the presence and absence of compounds containing platinum and bromine atoms were performed in order to asses the sensitization potential of these compounds. Plasmid DNA pBR322 was incubated with platinum (II) bromide, hydrogen hexabromoplatinate (IV), hydrogen hexahydroxyplatinate (IV) and sodium hexahydroxyplatinate (IV). Incubation was followed by X-ray or UV irradiations. It was found that amongst the sensitizers tested, during irradiations carried out in the presence of platinum (II) bromide, the highest levels of double strand breaks formation upon X-ray treatment were recorded. In contrast much less damage was induced by UV light. Data presented here suggests that this compound may be a promising radiosensitizer for cancer treatment