DNA-mediated Electron Transfer
Principal Investigator: Dr Marian Wolszczak (IARC)
Institute of Applied Radiation Chemistry, Technical Unversity, Wroblewskiego 15, 93-590 Lodz, Poland (IARC)
Our laboratory is specialized in the study of the electron transfer reaction induced by light and ionizing radiation. The pulse radiolysis and photolysis allow the investigations of reactive species in the time range from picoseconds to minutes in the spectral domain from 200 to 2000 nm and in a range temperatures from 1.6 to 300 K. The research area is focused on electron transfer process within polyelectrolyte chain including DNA duplex. A series of a trifunctional molecules consisting of two clasical intercalators linked by a polyamine chain showing itself site-specific interactions with DNA have been synthesised. The results of experimental studies on these and related systems have been analyzed within the framework of semiclassical electron transfer theory. Comparison of the results with those for other bridge-mediated electron transfer systems indicates that the p-stacked bases of DNA provide a better medium for electron transfer than the sigma bonded pathways of proteins and saturated hydrocarbons but do not function as a molecular wire. Current research focuses on the seeks to understand the mechanisms of the processes leading to the production of lethal agents to inactivate tumor cells during photodynamic therapy (PDT).
Influence of Ultrasound on DNA and on its Ability to Bind New Intercalators.
Principal Investigators: Dr Marian Wolszczak and Dr. Piotr Ulanski (IARC)
The search for new photochemically active substances able to intercalate to DNA is stimulated by the hopes raised by the recent progress in photodynamic anticancer therapy. One of the potentially interesting sensitizers currently studied in our lab is derivative of chlorine e6. Preliminary experiments indicate that the efficiency of intercalation of some substance to DNA (e.g. mitoxantrone) can be significantly increased by treatment with low-frequency ultrasound. It is planned to investigate this effect in more detail. In order to provide background for these studies, quantitative measurements on the action of low- and middle-frequency ultrasound (40 kHz – 1 MHz) on DNA in dilute aqueous solutions will be performed, with particular focus on the changes in molecular weight (strand breakage) and side effects (pyrolysis) that can affect the chemical structure.
Low Temperature ESR Studies of Primary Radiolysis Products in Diluted Aqueous Solutions of DNA and its Constituents
Principal Investigator: Dr Ewa Szajdzinska-Pietek (IARC)
The aim of this study is to follow reactivity of primary radiolysis products of water (OH, H, e-aq) toward biomolecules, using the technique of radiation cryochemistry with detection of transient species by ESR spectroscopy. The examined systems include diluted solutions of nucleobases, nucleotides, nucleosides, and DNA, vitrified by hyperquenching (with the rate ~106 K/s) liquid droplets of micrometer size. In these matrices, unlike commonly used polycrystalline systems, there is no phase separation between the solvent and the solute, so the indirect radiation effects can be followed by the steady-state method under conditions similar to those occurring in water-rich biological systems. The hyperquenched glasses are also more suitable model systems in comparison to ionic glasses (concentrated electrolyte solutions) used in the previous studies.
Protein damage induced by free radicals
Principal investigator: Dr Lidia Gebicka (IARC)
Free radicals can be generated either as by-products of normal cellular redox processes or via the interaction of cells and tissues with a variety of external processes and agents (e.g. ionizing radiation, photochemical reactions, action of xenobiotics). Radical-induced damage to proteins not only alter their properties, but also may initiate further redox reactions. Our preliminary studies show that some irradiated heme proteins exhibit new catalytic properties as well as consume important cellular reactants such as ascorbate and glutathione. It is planned to study radiation-induced peroxidatic activity of catalase and cytochrome c and reactions of radiolytically generated protein peroxides with various antioxidants in homogeneous and microheterogeneous systems. Steady-state g-radiolysis as well as pulse-radiolysis technique will be applied for these investigations.
COST P9 Workings group(s) of interest: