Jean-Christophe Poully

Upon UV photoabsorption by a vancomycin-receptor noncovalent complex, we report HCl formation in vancomycin and subsequent transfer to the receptor. Our data are consistent with a roaming atom mechanism.

Interaction with a single X-ray photon or carbon ion triggers the ejection of multiple valence electrons from a fibronectin peptide in the gas phase, cleaves backbone bonds but leaves disulfide bonds intact.

Radiation therapy is a medical treatment that uses high doses of radiation to kill or damage cancer cells. It works by damaging the DNA within the cancer cells, ultimately causing cell death. Radiotherapy can be used as a primary treatment, adjuvant treatment in combination with surgery or chemotherapy or palliative treatment to relieve symptoms in advanced cancer stages. Radiation therapy is constantly improving in order to enhance the effect on cancer cells and reduce the side effects on healthy tissues. Our results clearly demonstrate that proton therapy and, even more, carbon ion therapy appear as promising alternatives to overcome the radioresistance of various tumors thanks to less dependency on oxygen and a better ability to kill cancer stem cells. Interestingly, hadrons also retain the advantages of radiosensitization approaches. These data confirm the great ability of hadrons to spare healthy tissue near the tumor via various mechanisms (reduced lymphopenia, bystander effect, etc.). Technology and machine improvements such as image-guided radiotherapy or particle therapies can improve treatment quality and efficacy (dose deposition and biological effect) in tumors while increasingly sparing healthy tissues. Radiation biology can help to understand how cancer cells resist radiation (hypoxia, DNA repair mechanisms, stem cell status, cell cycle position, etc.), how normal tissues may display sensitivity to radiation and how radiation effects can be increased with either radiosensitizers or accelerated particles. All these research topics are under investigation within the ARCHADE research community in France. By focusing on these areas, radiotherapy can become more effective, targeted and safe, enhancing the overall treatment experience and outcomes for cancer patients. Our goal is to provide biological evidence of the therapeutic advantages of hadrontherapy, according to the tumor characteristics. This article aims to give an updated view of our research in radiation biology within the frame of the French “ARCHADE association” and new perspectives on research and treatment with the C400 multi-ions accelerator prototype.

The direct effects of ionizing radiation on antibiotics are largely unknown. Here, we report mass spectra of the cationic products of the irradiation of three antibiotics by carbon ions at 10.4 MeV kinetic energy. Carbon ion beams used in cancer treatments have this energy when they deliver the maximum dose to malignant cells. We find that upon single carbon ion collision, extensive fragmentation of antibiotics occurs, predominantly through channels similar to those observed in soft X‐ray photoabsorption. However, new product ions are also detected and attributed to the ability of MeV carbon ions to eject electrons from the molecular target in an unspecific manner. Proton transfer appears to play a key role in the dissociation dynamics of rifamycin and actinomycin, and it is complemented by sodium transfer in sodiated rifamycin and its dimer. Importantly, we report the first evidence for abundant loss of H from precursor ions, as well as for intramolecular cross‐linking triggered by carbon ion collision. All these processes most probably take place in the vibrationally hot electronic ground state of the molecular system.

Little is known regarding radiation-induced matrikines and the possible degradation of extracellular matrix following therapeutic irradiation. The goal of this study was to determine if irradiation can cut collagen proteins at specific sites, inducing potentially biologically active peptides against cartilage cells. Chondrocytes cultured as 3D models were evaluated for extracellular matrix production. Bystander molecules were analyzed in vitro in the conditioned medium of X-irradiated chondrocytes. Preferential breakage sites were analyzed in collagen polypeptide by mass spectrometry and resulting peptides were tested against chondrocytes. 3D models of chondrocytes displayed a light extracellular matrix able to maintain the structure. Irradiated and bystander chondrocytes showed a surprising radiation sensitivity at low doses, characteristic of the presence of bystander factors, particularly following 0.1 Gy. The glycine-proline peptidic bond was observed as a preferential cleavage site and a possible weakness of the collagen polypeptide after irradiation. From the 46 collagen peptides analyzed against chondrocytes culture, 20 peptides induced a reduction of viability and 5 peptides induced an increase of viability at the highest concentration between 0.1 and 1 µg/ml. We conclude that irradiation promoted a site-specific degradation of collagen. The potentially resulting peptides induce negative or positive regulations of chondrocyte growth. Taken together, these results suggest that ionizing radiation causes a degradation of cartilage proteins, leading to a functional unbalance of cartilage homeostasis after exposure, contributing to cartilage dysfunction.

Studying the direct effects of DNA irradiation is essential for understanding the impact of radiation on biological systems. Gas‐phase interactions are especially well suited to uncover the molecular mechanisms underlying these direct effects. Only relatively recently, isolated DNA oligonucleotides were irradiated by ionizing particles such as VUV or X‐ray photons or ion beams, and ionic products were analyzed by mass spectrometry. This article provides a comprehensive review of primarily experimental investigations in this field over the past decade, emphasizing the description of processes such as ionization, fragmentation, charge and hydrogen transfer triggered by photoabsorption or ion collision, and the recent progress made thanks to specific atomic photoabsorption. Then, we outline ongoing experimental developments notably involving ion‐mobility spectrometry, crossed beams or time‐resolved measurements. The discussion extends to potential research directions for the future.

Cross-linking is a fundamental molecular process that is highly important for many applications, in particular, to tune the properties of collagen-based biomaterials. Chemical reagents, the action of enzymes or physical factors such as heat or radiation can facilitate collagen cross-linking. Ionizing radiation has the advantages of being fast, efficient and free from potentially toxic reagents. Collagen cross-linking by ionizing radiation is thought to occur via a water-mediated pathway. In the past, synthesized collagen mimetic peptides have proven to be of great value for understanding the influence of the amino acid sequence on the stability of tertiary (fibrous) as well as secondary (triple helical) structures of collagen. Cross-linking of synthetic collagen mimetic peptides is often used for modifying the properties of biomaterials. In this work, for the first time, we apply radiation-induced cross-linking to synthetic collagen mimetic peptides and present an experimental and theoretical study of peptide hexamers consisting of two noncovalently bound triple helices in the absence of a molecular environment, i.e. in the gas phase. Our results show that X-ray photoabsorption of the hydroxylated hexamer leads to ionization and cross-linking of the two triple helices: thus, we found evidence that cross-linking can be achieved by ionizing radiation, without the presence of any reagent or water. We propose a cross-linking mechanism involving the creation of two radicals on hydroxyproline side-chains and their recombination, ultimately leading to covalent bond formation between the triple helices.

In biological tissues, ionizing radiation interacts with a variety of molecules and the consequences include cell killing and the modification of mechanical properties. Applications of biological radiation action are for instance radiotherapy, sterilization, or the tailoring of biomaterial properties. During the first femtoseconds to milliseconds after the initial radiation action, biomolecular systems typically respond by transfer of charge, atoms, or energy. In the condensed phase, it is usually very difficult to distinguish direct effects from indirect effects. A straightforward solution for this problem is the use of gas‐phase techniques, for instance from the field of mass spectrometry. In this review, we survey mainly experimental but also theoretical work, focusing on radiation‐induced intra‐ and inter‐molecular transfer of charge, atoms, and energy within biomolecular systems in the gas phase. Building blocks of DNA, proteins, and saccharides, but also antibiotics are considered. The emergence of general processes as well as their timescales and mechanisms are highlighted.

Understanding how charge and energy, as well as protons and hydrogen atoms, are transferred in molecular systems as a result of an electronic excitation is fundamental for understanding the interaction between ionizing radiation and biological matter on the molecular level. To localize the excitation at the atomic scale, it was chosen to target phosphorus atoms in the backbone of gas‐phase oligonucleotide anions and cations, by means of resonant photoabsorption at the L‐ and K‐edges. The ionic photoproducts of the excitation process were studied by a combination of mass spectrometry and X‐ray spectroscopy. The combination of absorption site selectivity and photoproduct sensitivity allowed the identification of X‐ray spectral signatures of specific processes. Moreover, charge and/or energy as well as H transfer from the backbone to nucleobases has been directly observed. Although the probability of one versus two H transfer following valence ionization depends on the nucleobase, ionization of sugar or phosphate groups at the carbon K‐edge or the phosphorus L‐edge mainly leads to single H transfer to protonated adenine. Moreover, our results indicate a surprising proton‐transfer process to specifically form protonated guanine after excitation or ionization of P 2p electrons.