Contribution of Indirect Action to Radiation-Induced Mammalian Cell Inactivation: Dependence on Photon Energy and Heavy-Ion LET

Abstract

The contribution of indirect action mediated by OH radicals to cell inactivation by ionizing radiations was evaluated for photons over the energy range from 12.4 keV to 1.25 MeV and for heavy ions over the linear energy transfer (LET) range from 20 keV/microm to 440 keV/microm by applying competition kinetics analysis using the OH radical scavenger DMSO. The maximum level of protection provided by DMSO (the protectable fraction) decreased with decreasing photon energy down to 63% at 12.4 keV. For heavy ions, a protectable fraction of 65% was found for an LET of around 200 keV/microm; above that LET, the value stayed the same. The reaction rate of OH radicals with intracellular molecules responsible for cell inactivation was nearly constant for photon inactivation, while for the heavy ions, the rate increased with increasing LET, suggesting a reaction with the densely produced OH radicals by high-LET ions. Using the protectable fraction, the cell killing was separated into two components, one due to indirect action and the other due to direct action. The inactivation efficiency for indirect action was greater than that for direct action over the photon energy range and the ion LET range tested. A significant contribution of direct action was also found for the increased RBE in the low photon energy region.

Response of cancer stem-like cells and non-stem cancer cells to proton and γ-ray irradiation

“…Clustered damages can involve SSBs, DSBs, base damages, or even more complex associations including multiple closely scattered DSBs. The greater the extent of damages, the more difficult it is to be repaired, thereby the radiation damage of protons is larger than that of photons [31].…”

Refinement of the Dichlorofluorescein Assay for Flow Cytometric Measurement of Reactive Oxygen Species in Irradiated and Bystander Cell Populations

“…Approximately 65% of intracellular damage caused by low-LET ionizing radiation such as X rays and ␥ rays occurs indirectly through radiolytic production of ROS (1). Oxidative damage to DNA can result in a variety of lesions, including base damage, inter-and intrastrand crosslinks, DNA-protein crosslinks, single-strand breaks and doublestrand breaks (2,3).…”

OH Radicals from the Indirect Actions of X-Rays Induce Cell Lethality and Mediate the Majority of the Oxygen Enhancement Effect

“…, k s and k DMSO were defined as the concentration of cellular reaction sites (target cellular molecules) responsible for cell killing (M), the reaction constant of OH radicals with target cellular molecules and that of OH radicals with DMSO (M À1 s À1 ), respectively (1,5). IA and DA are the indirect and direct action components that together constitute the ''effective dose'' contribution to cell killing.…”

“…Conversely, the lethal damage induced by the direct action of X rays are less affected by oxygen concentration. Ó 2013 by Radiation Research Society INTRODUCTION Over the past few years, we published studies on the role of free radicals in the biological response to heavy-ion radiation (1)(2)(3)(4)(5). It is well established, that X rays induce DNA damage by two interacting mechanisms: Indirect actions which are mediated by radicals arising from water radiolysis; and direct actions due to the deposition of radiation energy directly on DNA.…”