Oxygen Effect on 0-30 eV Electron Damage to DNA Under Different Hydration Levels: Base and Clustered Lesions, Strand Breaks and Crosslinks.

Studies on radiosensitization of biological damage by O began about a century ago and it remains one of the most significant subjects in radiobiology. It has been related to increased production of oxygen radicals and other reactive metabolites, but only recently to the action of the numerous low-energy electrons (LEEs: 0-30 eV) produced by ionizing radiation. We provide the first complete set of G-values (yields of specific products per energy deposited) for all conformational damages induced to plasmid DNA by LEEs (G (O)) and 1.

Comparisons between the Direct and Indirect Effect of 1.5 keV X-rays and 0-30 eV Electrons on DNA: Base Lesions, Stand Breaks, Cross-Links, and Cluster Damages.

The interaction of low energy electrons (LEEs; 1-30 eV) with genomic material can induce multiple types of damage that may cause the loss of genetic information, mutations, genome instability, and cell death. For all damages measurable by electrophoresis, we provide the first complete set of -values (yield of a specific product per energy deposited) induced in plasmid DNA by the direct and indirect effects of LEEs () and 1.5 keV X-rays () under identical conditions.

Binding energies of CD4 and fragment species to Pt(111): Implications for measurements of anion electron stimulated desorption.

We consider the electron stimulated desorption, via dissociative electron attachment, of anionic species from thin condensed CD4 films deposited on a Pt substrate and compare experimentally observed desorption yields with density functional theory calculations of the binding energies of various anionic and neutral moieties to Pt(111). Certain species (which can be considered chemisorbed) exhibit very high binding energies and large charge transfer with the substrate. Other "physisorbed" species have much lower binding energies.

How a Single 5 eV Electron Can Induce Double-Strand Breaks in DNA: A Time-Dependent Density Functional Theory Study.

Low-energy (<20 eV) electrons (LEEs) can resonantly interact with DNA to form transient anions (TAs) of fundamental units, inducing single-strand breaks (SSBs), and cluster damage, such as double-strand breaks (DSBs). Shape resonances, which arise from electron capture in a previously unfilled orbital, can induce only a SSB, whereas a single core-excited resonance (i.e.

Electron-Induced Damage by UV Photolysis of DNA Attached to Gold Nanoparticles.

Photolysis of DNA attached to gold nanoparticles (AuNPs) with ultraviolet (UV) photons induces DNA damage. The release of nucleobases (Cyt, Gua, Ade, and Thy) from DNA was the major reaction (99%) with an approximately equal release of pyrimidines and purines. This reaction contributes to the formation of abasic sites in DNA.

DNA Protection against Damages Induced by Low-Energy Electrons: Absolute Cross Sections for Arginine-DNA Complexes.

Histone proteins protect cellular DNA from radiation damage. We find that arginine, a major component of histone proteins, protects DNA from lesions induced by low-energy secondary electrons generated by radiation. Thin films of 7 ± 2, 12 ± 4, and 17 ± 4 nm thicknesses containing arginine-plasmid-DNA complexes in molar ratio of [Arg]/[PO] = 16 are irradiated in vacuum with 5 and 10 eV electrons.

Mechanisms of Nanoscale Radiation Enhancement by Metal Nanoparticles: Role of Low Energy Electrons.

Metal nanoparticles are considered as highly promising radiosensitizers in cancer radiotherapy. Understanding their radiosensitization mechanisms is critical for future clinical applications. This review is focused on the initial energy deposition by short-range Auger electrons; when high energy radiation is absorbed by gold nanoparticles (GNPs) located near vital biomolecules; such as DNA.

DNA radiosensitization by terpyridine-platinum: damage induced by 5 and 10 eV transient anions.

Chemoradiation therapy (CRT), which combines a chemotherapeutic drug with ionizing radiation (IR), is the most common cancer treatment. At the molecular level, the binding of Pt-drugs to DNA sensitizes cancer cells to IR, mostly by increasing the damage induced by secondary low-energy (0-20 eV) electrons (LEEs). We investigate such enhancements by binding terpyridine-platinum (Tpy-Pt) to supercoiled plasmid DNA.

behavior of [Cu]NOTA-terpyridine platinum, a novel chemo-radio-theranostic agent for imaging, and therapy of colorectal cancer.

To overcome resistance to chemotherapy for colorectal cancer, we propose to validate a novel terpyridine-platinum (TP) compound radiolabeled with the radio-theranostic isotope Cu. stability, biodistribution, PET imaging, tumor growth delay, toxicity and dosimetry of [Cu]NOTA-C3-TP were determined. The current experimental studies show that [Cu]NOTA-C3-TP is stable , rapidly eliminated by the kidneys and has a promising tumor uptake ranging from 1.

Low-Energy Electron Damage to Plasmid DNA in Thin Films: Dependence on Substrates, Surface Density, Charging, Environment, and Uniformity.

The interaction of low-energy electrons (LEEs) with DNA plays a significant role in the mechanisms leading to biological damage induced by ionizing radiation, particularly in radiotherapy, and its sensitization by chemotherapeutic drugs and nanoparticles. Plasmids constitute the form of DNA found in mitochondria and appear as a suitable model of genomic DNA. In a search for the best LEE targets, damage was induced to plasmids, in thin films in vacuum, by 6, 10, and 100 eV electrons under single collision conditions.

Shape Resonances in DNA: Nucleobase Release, Reduction, and Dideoxynucleoside Products Induced by 1.3 to 2.3 eV Electrons.

Understanding the details of DNA damage caused by high-energy particles or photons is complicated by the multitude of reactive species, arising from the ionization and dissociation of HO, DNA, and protein. In this work, oligonucleotides (ODNs) are irradiated with a beam of low-energy electrons of 1.3 to 2.

Estimation of the Internal Dose Imparted by F-Fluorodeoxyglucose to Tissues by Using Fricke Dosimetry in a Phantom and Positron Emission Tomography.

Purpose: Assessment of the radiation dose delivered to a tumor and different organs is a major issue when using radiolabelled compounds for diagnostic imaging or endoradiotherapy. The present article reports on a study to correlate the mean F-fluorodeoxyglucose (F-FDG) activity in different tissues measured in a mouse model by positron emission tomography (PET) imaging, with the dose assessed by Fricke dosimetry.

Methods: The dose-response relationship of the Fricke dosimeter and PET data was determined at different times after adding F-FDG (0-80 MBq) to a Fricke solution (1 mM ferrous ammonium sulfate in 0.

Damage Induced to DNA and Its Constituents by 0-3 eV UV Photoelectrons.

The complex physical and chemical interactions between DNA and 0-3 eV electrons released by UV photoionization can lead to the formation of various lesions such as base modifications and cleavage, crosslinks and single strand breaks. Furthermore, in the presence of platinum chemotherapeutic agents, these electrons can cause clustered lesions, including double strand breaks. We explain the mechanisms responsible for these damages via the production 0-3 eV electrons by UVC radiation, and by UV photons of any wavelengths, when they are produced by photoemission from nanoparticles lying within about 10 nm from DNA.

Profiling DNA Damage Induced by the Irradiation of DNA with Gold Nanoparticles.

The presence of gold nanoparticles (AuNPs) greatly enhances the formation of DNA damage when exposed to therapeutic X-rays. Three types of DNA damage are assessed in irradiated DNA by enzymatic digestion coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The major type of damage is release of the four nonmodified nucleobases, with a bias toward the release of cytosine and thymine.

Design, Synthesis, and Cytotoxicity Assessment of [Cu]Cu-NOTA-Terpyridine Platinum Conjugate: A Novel Chemoradiotherapeutic Agent with Flexible Linker.

Maximum benefits of chemoradiation therapy with platinum-based compounds are expected if the radiation and the drug are localized simultaneously in cancer cells. To optimize this concomitant effect, we developed the novel chemoradiotherapeutic agent [Cu]Cu-NOTA-C3-TP by conjugating, via a short flexible alkyl chain spacer (C3), a terpyridine platinum (TP) moiety to a NOTA chelator complexed with copper-64 (Cu). The decay of Cu produces numerous low-energy electrons, enabling the Cu-conjugate to deliver radiation energy close to TP, which intercalates into G-quadruplex DNA.

Low-Energy Electron Damage to Condensed-Phase DNA and Its Constituents.

The complex physical and chemical reactions between the large number of low-energy (0-30 eV) electrons (LEEs) released by high energy radiation interacting with genetic material can lead to the formation of various DNA lesions such as crosslinks, single strand breaks, base modifications, and cleavage, as well as double strand breaks and other cluster damages. When crosslinks and cluster damages cannot be repaired by the cell, they can cause genetic loss of information, mutations, apoptosis, and promote genomic instability. Through the efforts of many research groups in the past two decades, the study of the interaction between LEEs and DNA under different experimental conditions has unveiled some of the main mechanisms responsible for these damages.

Chemical transformation of molecular ices containing NO and CD by low energy electrons: New chemical species of astronomical interest.

We have employed electron stimulated desorption (ESD) and x-ray photoelectron spectroscopy (XPS) to study the chemical species generated from multilayer films of NO, CD, and mixtures thereof (i.e., NO/CD) by the impact of low energy electrons with energies between 30 and 70 eV.

High Cytotoxic Effect by Combining Copper-64 with a NOTA-Terpyridine Platinum Conjugate.

Terpyridine platinum (TP)-based chemotherapeutic agents target three-dimensional structures on DNA known as G-quadruplexes. We report the rational design and synthesis of a TP conjugate combined with copper-64 (Cu), the decay characteristics of which include emission of β and Auger electrons for radiotherapy and β particles for positron emission tomography (PET) imaging. The present experimental studies show that the novel [Cu]Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-TP is stable, permitting selective killing of cancer cells.

Early Events in Radiobiology: Isolated and Cluster DNA Damage Induced by Initial Cations and Nonionizing Secondary Electrons.

Radiobiological damage is principally triggered by an initial cation and a secondary electron (SE). We address the fundamental questions: What lesions are first produced in DNA by this cation or nonionizing SE? What are their relative contributions to isolated and potentially lethal cluster lesions? Five monolayer films of dry plasmid DNA deposited on graphite or tantalum substrates are bombarded by 0.1-100 eV electrons in a vacuum.

Concomitant Chemoradiation Therapy with Gold Nanoparticles and Platinum Drugs Co-Encapsulated in Liposomes.

A liposomal formulation of gold nanoparticles (GNPs) and carboplatin, named LipoGold, was produced with the staggered herringbone microfluidic method. The radiosensitizing potential of LipoGold and similar concentrations of non-liposomal GNPs, carboplatin and oxaliplatin was evaluated in vitro with the human colorectal cancer cell line HCT116 in a clonogenic assay. Progression of HCT116 tumor implanted subcutaneously in NU/NU mice was monitored after an irradiation of 10 Gy combined with either LipoGold, GNPs or carboplatin injected directly into the tumor by convection-enhanced delivery.

Role of Transient Anions in Chemoradiation Therapy: Base Modifications, Cross-Links, and Cluster Damages Induced to Cisplatin-DNA Complexes by 1-20 eV Electrons.

The molecular mechanism of platinum-based drugs in concomitant chemoradiation therapy relies on enhancement of DNA damage in cancer cells, particularly that of detrimental clustered lesions and cross-links induced by the abundant low-energy electrons (LEEs) generated by ionizing radiation. We provide the complete 1-20 eV electron-energy dependence of the yields of all conformational LEE-induced lesions to biological DNA, when it binds to five molecules of the chemotherapeutic drug cisplatin. Recording at 1 eV intervals clearly show that the enhancement of all lesions is particularly intense at the energies of core-excited transient molecular anions (i.

Convection-Enhanced Delivery in Malignant Gliomas: A Review of Toxicity and Efficacy.

Malignant gliomas are undifferentiated or anaplastic gliomas. They remain incurable with a multitude of modalities, including surgery, radiation, chemotherapy, and alternating electric field therapy. Convection-enhanced delivery (CED) is a local treatment that can bypass the blood-brain barrier and increase the tumor uptake of therapeutic agents, while decreasing exposure to healthy tissues.

Clustered DNA Damages induced by 0.5 to 30 eV Electrons.

Low-energy electrons (LEEs) of energies ≤30 eV are generated in large quantities by ionizing radiation. These electrons can damage DNA; particularly, they can induce the more detrimental clustered lesions in cells. This type of lesions, which are responsible for a large portion of the genotoxic stress generated by ionizing radiation, is described in the Introduction.