Grant: Discovery Grants Program - Individual

Secondary electrons are the most abundant species produced by high energy radiation. The vast majority have energies below 30 eV and play key roles in diverse fundamental and applied fields. To understand and control the action of such low energy electrons (LEEs), information is needed on the type and magnitude of the processes involved in the material of interest. The proposed research focuses on the fundamental physical and chemical processes relevant to radiobiology, i.e., the study of the action of ionizing radiation on living systems that underpins both radioprotection and radiotherapy. Since radiation effects on DNA are central to radiobiology, our general objective for the next five years is to provide a description of the interaction of LEEs (0-30 eV) with DNA, and the subsequent induced chemistry, under conditions progressively closer to those of living cells. We will identify and quantify LEE-induced products and reaction pathways in targets of increasing complexity, i.e., lyophilized, or self-assembled films of oligonucleotides, plasmid and calf thymus DNA, plasmids intercalated with histone constituents, oligonucleotides wrapped around histone proteins forming nucleosomes, nuclear DNA within HeLa cells and plasmids bound to various radiosensitizers. Thin films deposited on Tantalum (Ta) or graphite substrates will be irradiated, under vacuum with monoenergetic LEEs, to obtain the thickness and energy dependence (yield functions) of damage yields. The type of damage, will be determined and quantitated by electrophoresis or HPLC/MS-MS. The results of vacuum experiments will be compared to those obtained under atmospheric gases at different humidity levels, or within the nucleus of HeLa cancer cells. In the latter two experiments, the LEE sources will be either UV- or X-ray photoelectrons from a Ta substrate or gold nanoparticles (GNPs) internalised within cell nuclei. Electron- and UV-induced products will be separately identified by changing the UV wavelength. Plasmid DNA pre-bombarded with LEEs will be inserted into bacteria to correlate loss of cellular transformation to damage yield functions. We will attempt to identify all mechanisms involved, including the formation of transient anions. The proposed research should provide 1) concepts needed to understand the physical chemistry of secondary electrons in large biomolecules, 2) insight into the mechanisms of action of LEEs with cellular DNA, 3) detailed descriptions of the role of chromatin components, radiosensitizer and GNPs on DNA damage and 4) substantial contributions to UV photoelectron-induced reactions in nanoparticle-DNA complexes. Such information finds applications in many fields, e.g., carcinogenesis, laser phototherapy, targeted radiotherapy, LEE microscopy and radiation protection on earth and in space. This program will promote high quality research in the field of LEE-biomolecule interactions and provide a stimulating training environment.