Exploring Radiation Chemistry: Implication to Radiation Biology and Radiotherapy

2024 | Vol-1 | Issue-1 | Date of Submission: | Date of Publication:

Abstract

Our ongoing studies of irradiated DNA have led to a comprehensive model of radiation-induced DNA damage. This model describes physicochemical events from the initial deposition of energy to DNA ion-radical-excited state formation through hole and electron transfer, to chemical events involving free radical processes that lead to secondary radicals which result in DNA damage such as base and sugar damage, strand breaks (sb), and concurrent base release. The very high global concentration (65 to 220 mg/ml) of macromolecules (DNA, RNA, proteins etc.) in the nucleus makes the role of direct-type effects of radiation in cells of crucial importance. DNA-radicals including sugar radicals are the precursors of radiation-induced sb and clustered damage. Our studies employing synthesis (Dembinski group, OU; Wnuk group, FIU, Miami), electron spin resonance (ESR) spectroscopy at low temperatures (LT) (OU), picosec pulse radiolysis at RT (Prof. Mostafavi, University of Paris, ELYSE, France), measurements of unaltered base release in the same samples at RT using HPLC (OU), tandem mass spectrometry at RT (Dizdaroglu group, NIST), theoretical (DFT) calculations of radical mechanisms (OU and IIT-Mumbai), and Geant4-DNA monte-carlo calculations (With JHU, Maryland) have unraveled mechanisms of DNA-sugar radical formation via direct-type effects, viz. (i) sugar radical formation via excitation of DNA base cation radicals and (ii) sb via dissociative electron attachment induced by low energy electrons (LEE). Moreover, we are investigating the effect of chemical radiomodifiers (Seal-Coathup, UCF, Orlando) on the frank DNA-radicals yields’ and ROS that are precursors of sb and of clustered damage. These results are of potential significance to radiobiology and radiotherapy.