Key biological mechanisms involved in high-LET radiation therapies with a focus on DNA damage and repair.

DNA damage and repair studies are at the core of the radiation biology field and represent also the fundamental principles informing radiation therapy (RT). DNA damage levels are a function of radiation dose, whereas the type of damage and biological effects such as DNA damage complexity, depend on radiation quality that is linear energy transfer (LET). Both levels and types of DNA damage determine cell fate, which can include necrosis, apoptosis, senescence or autophagy. Herein, we present an overview of current RT modalities in the light of DNA damage and repair with emphasis on medium to high-LET radiation. Proton radiation is discussed along with its new adaptation of FLASH RT. RT based on α-particles includes brachytherapy and nuclear-RT, that is proton-boron capture therapy (PBCT) and boron-neutron capture therapy (BNCT). We also discuss carbon ion therapy along with combinatorial immune-based therapies and high-LET RT. For each RT modality, we summarise relevant DNA damage studies. Finally, we provide an update of the role of DNA repair in high-LET RT and we explore the biological responses triggered by differential LET and dose.

A Mathematical Radiobiological Model (MRM) to Predict Complex DNA Damage and Cell Survival for Ionizing Particle Radiations of Varying Quality.

Predicting radiobiological effects is important in different areas of basic or clinical applications using ionizing radiation (IR); for example, towards optimizing radiation protection or radiation therapy protocols. In this case, we utilized as a basis the 'MultiScale Approach (MSA)' model and developed an integrated mathematical radiobiological model (MRM) with several modifications and improvements. Based on this new adaptation of the MSA model, we have predicted cell-specific levels of initial complex DNA damage and cell survival for irradiation with 11Β, 12C, 14Ν, 16Ο, 20Νe, 40Αr, 28Si and 56Fe ions by using only three input parameters (particle's LET and two cell-specific parameters: the cross sectional area of each cell nucleus and its genome size). The model-predicted survival curves are in good agreement with the experimental ones. The particle Relative Biological Effectiveness (RBE) and Oxygen Enhancement Ratio (OER) are also calculated in a very satisfactory way. The proposed integrated MRM model (within current limitations) can be a useful tool for the assessment of radiation biological damage for ions used in hadron-beam radiation therapy or radiation protection purposes.

Temporal investigation of radionuclides and heavy metals in a coastal mining area at Ierissos Gulf, Greece.

Vertical variations of radionuclides, trace metals, and major elements were determined in two sediment cores, which were collected in the marine environment of Ierissos Gulf near Stratoni's mining area. The enrichment factors (EFs) were also estimated and provided moderately severe to extremely severe enrichment for most trace elements and Mn, describing the anthropogenic influence in the gulf during the previous century. According to the applied dating models based on 210Pb and 137Cs, the effect in the marine sediment due to the exploitation of pyrite for the production of sulfuric acid during 1912-1920 was observed. Additionally, the decrease of mining activity during 1935-1945 due to the Second World War and the type of ore exploitation, the alteration of the exploited ores, and the construction and operation of Olympiada's floatation plant during 1950-1970 were identified. The end of tailing discharging into the marine environment during 1980-2010 was also noted.

Development and optimization of an underwater in-situ cerium bromide spectrometer for radioactivity measurements in the aquatic environment.

A new medium resolution gamma-ray spectrometer consisting of a cerium bromide (CeBr3) crystal (2˝ x 2˝), is developed and optimized for radioactivity measurements in aquatic environments. This apparatus named GeoMAREA (Gamma-ray spectrometer for in-situ Marine Environmental Applications) is designed to control and prevent radio-contaminants in aquatic environments as well as to estimate the variation of natural radionuclides in marine systems for studying oceanographic processes. The system offers activity concentrations in Bq/m3 for detected gamma-ray emitters in the energy range from 150 to 2600 keV, and can provide sequential continuous monitoring data in a stand-alone mode or it can be integrated in stationary/mobile platforms for (near) real-time applications. The photopeak efficiency values were estimated via the MCNPΧ code. Two experimental points were used to validate the theoretical estimations by deploying the system in a water tank with diluted reference sources such us Caesium-137 (137Cs) and Potassium-40 (40K). The system was subsequently deployed in the field along with a conductivity-temperature (CT) sensor, to measure 40K and radon daughters in a region where submarine groundwater discharges (Anavalos, Kiveri, Greece) are present. The experimental calibration data was utilized to provide a first estimation for the background contribution around the photopeak of 40K, attributed to the Cerium Bromide (CeBr3) intrinsic activity.

Historical trends and assessment of radionuclides and heavy metals in sediments near an abandoned mine, Lavrio, Greece.

Two sediment cores (coastal and offshore) and surface sediments were collected near an abandoned mine area in the marine environment of Oxygono Bay at Lavreotiki peninsula to investigate temporal and spatial variations among radionuclides and trace metals/major elements. Lavreotiki was and still is well known for the mining and metallurgical activities, which lasted from ancient times to nowadays (early 1980s). Gamma-ray and X-ray fluorescence measurements were held to determine the radionuclide and trace metal/major element concentrations, respectively. The sedimentation rate at Oxygono Bay coastal core was determined using the 210Pb and 137Cs tracers, while the enrichment factors were estimated to assess the anthropogenic influence due to metals in a spatial (surface sediments) and a temporal (coastal core sediments) basis. The mass flux at the coastal core was utilized to provide a baseline information at Lavreotiki peninsula. The trace metal/major element profiles were indeed associated with the mining activity in the area, revealing the mining history. The ERICA Tool was incorporated to estimate the dose rates due to natural and 137Cs radioactivity in the marine organisms and the values were found below the screening levels.