C. Le Sech

Enhancement of radiation effect by heavy elements

The enhancement of radiobiological effects by heavy elements is reviewed. As an underlying mechanism, Auger effects have been stressed which can be induced via inner-shell photoabsorption or via excitation and/or ionization by secondary electrons. Latter channel of Auger induction expands the applicability of Auger enhancing phenomena to electron and hadron therapy. After discussion on the required characteristics for radiosensitizers, possibility of nanoparticles of Au or Pt is mentioned since they could be synthesized or modified as ideal radiosensitizers.

Mammalian cells loaded with platinum-containing molecules are sensitized to fast atomic ions

Purpose: This work investigates whether a synergy in cell death induction exists in combining atomic ions irradiation and addition of platinum salts. Such a synergy could be of interest in view of new cancer therapy protocol based on atomic ions – hadrontherapy – with the addition of radiosensitizing agents containing high-Z atoms. The experiment consists in irradiating by fast ions cultured cells previously exposed to dichloroterpyridine Platinum (PtTC) and analyzing cell survival by a colony-forming assay. Materials and methods: Chinese Hamster Ovary (CHO) cells were incubated for six hours in medium containing 350 μM PtTC, and then irradiated by fast ions C6+ and He2+, with Linear Energy Transfer (LET) within range 2–70 keV/μm. In some experiments, dimethyl sulfoxide (DMSO) was added to investigate the role of free radicals. The intracellular localization of platinum was determined by Nano Secondary Ion Mass Spectroscopy (Nano-SIMS). Results: For all LET examined, cell death rate is largely enhanced when irradiating in presence of PtTC. At fixed irradiation dose, cell death rate increases with increasing LET, while the platinum relative effect is larger at low LET. Conclusion: This finding suggests that hadrontherapy or protontherapy therapeutic index could be improved by combining irradiation procedure with concomitant chemotherapy protocols using platinum salts.

DNA strand breaks induced by low keV energy heavy ions

We present some results on the interaction of low energy atomic ions with DNA. Experiments consist of irradiation of dried DNA in vacuum with Ar ions at low keV energies for different time intervals. The DNA is placed back in solution and analysed by agarose gel electrophoresis. These experiments demonstrated the production of single and double strand breaks. The induction of these lesions could be due to several processes: direct collisions with DNA constituent atoms resulting in displacements, cascade recoil collisions of the constituent atoms, electron transfer processes between the ion and the DNA as well as breaks induced by molecular excitation and secondary electron interactions. Here we briefly discuss some aspects of direct and recoil collision processes.

Irradiation of DNA loaded with platinum containing molecules by fast atomic ions C6+ and Fe26+

Purpose: In order to study the role of the Linear Energy Transfer (LET) of fast atomic ions in platinum-DNA complexes inducing breaks, DNA Plasmids were irradiated by C6+ and Fe26+ ions. Material and methods: DNA Plasmids (pBR322) loaded with different amounts of platinum contained in a terpyridine-platinum molecule (PtTC) were irradiated by C6+ ions and Fe26+ ions. The LET values ranged between 13.4 keV/μm and 550 keV/μm. In some experiments, dimethyl sulfoxide (DMSO) was added. Results: In all experiments, a significant increase in DNA strand breaks was observed when platinum was present. The yield of breaks induced per Gray decreased when the LET increased. The yield of single and double strand breaks per plasmid per track increased with the LET, indicating that the number of DNA breaks per Gray was related to the number of tracks through the medium. Conclusions: These findings show that more DNA breaks are induced by atomic ions when platinum is present. This effect increases for low LET heavy atoms. As DSB induction may induce cell death, these results could open new perspectives with the association of hadrontherapy and chemotherapy. Thus the therapeutic index might be improved by loading the tumour with platinum salts.

Fast He2+ ion irradiation of DNA loaded with platinum-containing molecules

Purpose: The association of radiotherapy and chemotherapy is an attractive approach to improve the therapeutic index of the treatment of tumors. A lot of work has been devoted to investigate the effects of X-ray, γ-ray and neutron irradiation of DNA or living cells loaded with different chemical compounds containing heavy atoms like platinum. No such studies exist presently when fast atomic ions are chosen as ionizing particles. In the present work, we investigate quantitatively the increase of DNA breaks in complexes of plasmid-DNA loaded with platinum atoms under irradiation by fast atomic He2+ ions. Materials and methods: DNA Plasmids (pBR322) are incubated in solutions containing different concentrations of terpyridine platinum (PtTC). In some preparations, dimethyl sulfoxide (DMSO), a free radical scavenger, has been added in order to investigate the role of the free radicals. The complexes of DNA plasmids loaded with high-Z atoms are irradiated under atmospheric conditions by He2+ ions at an energy of 143 MeV/amu and a linear energy transfert (LET) of 2.24 keV/μm. Analysis of DNA damage – single and double strand breaks – is made by electrophoresis on agarose gels. Results: The results show a significant increase in DNA strand breaks when platinum is present, indicating a radiosensitization by the high Z atoms. The increase in DNA damages is attributed to inner-shell ionization of a platinum atom by secondary electrons emitted along the He2+ tracks followed by an Auger deexcitation, leading, thus, to a local amplification of the radiative effects close to the DNA. The contributions of scavengeable – solvant mediated – indirect effects and non-scavengeable effects (direct ionization) are quantitatively evaluated. Conclusion: Enhancement of DNA breaks in plasmids loaded with heavy atoms like platinum and irradiated by atomic ions are observed. This finding suggests an enhancement of cell death rate will occur under irradiation by atomic ions when the cells contain high-Z atoms located close to DNA due to the increase of the DNA breaks.

Accurate analytic wavefunctions for two-electron atoms

Simple analytic two variational parameters wavefunctions for the ground state of , He, , , atom (ions) are proposed. These functions fulfil the cusp conditions at the singularities of the Coulombic field, and include the correct behaviour for large interparticle separations. The accuracy of the calculated energies is found to be about . These functions should be useful for the computation of the cross section of inelastic processes involving two-electron systems.

Photosensitization of plasmid-DNA loaded with platinum nano-particles and irradiated by low energy X-rays

Damage in DNA plasmids (pBR322) loaded with platinum nanoparticles (NP-Pt) DNA-NP and irradiated with monochromatic X-rays tuned to the resonant photoabsorption energy of the LIII and MIII electronic inner-shell of platinum - respectively 11556 eV and 2649 eV - and off-resonant X-rays - 11536 eV and 2639 eV- is investigated. In all the experiments, an enhancement of the single and double strand break - SSB and DSB - yields is observed when NP-Pt are present. Amplification effects are almost similar for the irradiations performed at on and off the L or M shell resonance suggesting that a non resonant mechanism is responsible for the major part of the DNA breaks enhancement.The amount of DNA breaks measured in the present work is compared to the results in similar experiments made with complexes of plasmid-DNA containing platinum molecule : chloroterpyridine platinum (PtTC). The average number of PtTC molecules in the solution is the same as in the experiments made with NP-Pt in order to study a possible difference in the radiosensitization efficiency when the high-Z atoms are clustered (NP-Pt) or dispersed in the system (PtTC). A mechanism is suggested involving photoelectrons which can efficiently ionize the platinum atoms. These results are consistent with those observed when DNA-NP complexes are irradiated by fast atomic ions. These findings suggest that any nanoparticle made of high-Z atoms might behaves as radiation enhancer whatever the ionizing radiation is electromagnetic or charged particle source.

Simple correlated wavefunction for two-electron diatomic molecules. Application to H2 and He2+2 systems

Abstract In the present work we show that one can build accurate wavefunctions depending upon few variational parameters for ground and excited states of two-electron diatomic systems. Such simple wavefunctions could be useful in collisional problems. A convenient expression to compute the energy is also given using the first Green theorem.

Nano-Sensitization under gamma rays and fast ion radiation

The use of heavy compounds to enhance radiation induced damage is a promising approach to improve the therapeutic index of radiotherapy. In order to quantify and control the effects of these radiosensitizers, it is of fundamental interest to describe the elementary processes which take place at the molecular level. Using DNA as a probe, we present a comparison of the damage induced in the presence of platinum compounds exposed to different types of ionizing radiation. We present the results obtained with gamma rays (Linear Energy Transfer (LET) = 0.2 keV.µm -1 ), fast helium ions He 2+ (LET = 2.3 keV.µm -1 ) and fast carbon ions C 6+ (LET =13 keV.µm -1 and LET=110 keV.μm -1 ). The efficiency of two different sensitizers was measured: platinum based molecules (the chloroterpyridine platinum - PtTC) and platinum nanoparticles (PtNP). These experiments show that the two sensitizers are efficiently amplifying molecular damage under photon or ion irradiation. Experiments with a radical scavenger confirmed that these damages are mediated by free radicals for more than 90%. More interestingly, the induction of complex damage, the most lethal for the cells, is amplified by a factor of 1.5 on average if platinum (PtTC and PtNP) is present. As already known, the induction of complex damages increases also with the radiation LET. So, finally, the most significant enhancement of complex damage is observed when ion radiation is combined with platinum induced sensitization.

The pluvinage method for alkali dimers: Calculations for the Σ excited states of Na2 up to the (3p + 3p) dissociation limit

Abstract Twenty-six Σ potential curves of Na 2 are computed using a correlated orbital method. Rydberg series are seen converging to a bonding or antibonding Na 2 + curve. Crossings with the Na 2 + X 2 Σ g + curve occur for the 8 1 Σ g + , 6 1 Σ u + , 6 3 Σ u + , 7 3 Σ u + , 1 1 Σ u − , 8 3 Σ u + curves at internuclear distances R = 5.4, 6.5, 6.6, 8.2, 9.0 and 9.4 au, respectively.