Alegría Montoro’s research while affiliated with Hospital Universitari i Politècnic la Fe and other places

In previous RENEB interlaboratory comparisons based on the manual scoring of dicentric chromosomes, a tendency for systematic overestimation for doses > 2.5 Gy was found. However, these exercises included only very few doses in the high dose range, and they were heterogeneous in terms of radiation quality and evaluation mode, and comparable only to a limited extent. Here, this presumed deviation was explored by investigating three doses > 2.5 Gy. Blood samples were irradiated (2.56, 3.41 and 4.54 Gy) using a ⁶⁰Co source and sent to 14 member laboratories of the RENEB network, which performed the dicentric chromosome assay (manual and/or semi-automatic scoring) and reported dose estimates. Most participants provided estimates that agreed very well with the physical reference doses and all provided dose estimates were in the correct clinical category (> 2 Gy). The previously observed tendency for a systematic bias across all laboratories was not confirmed. However, tendencies for systematic underestimation were detected for dose estimations for reference doses given in terms of absorbed dose to blood and for some participants, a laboratory-specific trend of systematic under- or overestimation was observed. The importance of regularly performed quality checks for a broad dose range became obvious to avoid misinterpretation of results.

Ionizing radiation has been a critical tool in various fields, such as medicine, agriculture, and energy production, since its discovery in 1895. While its applications—particularly in cancer treatment and diagnostics—offer significant benefits, ionizing radiation also poses risks due to its potential to cause molecular and cellular damage. This damage can occur through the direct ionization of biological macromolecules, such as deoxyribonucleic acid (DNA), or indirectly through the radiolysis of water, which generates reactive oxygen species (ROS) that further damage cellular components. Radioprotectors, compounds that protect against radiation-induced damage, have been extensively researched since World War II. These agents work by enhancing DNA repair, scavenging free radicals, and boosting antioxidant defenses, thereby protecting healthy tissues. Furthermore, some radioprotective agents also stimulate DNA repair mechanisms even after radiation exposure, aiding in recovery from radiation-induced damage. This article explores the molecular mechanisms of radiation-induced damage, focusing on both direct and indirect effects on DNA, and discusses the role of radioprotectors, their mechanisms of action, and recent advancements in the field. The findings underscore the importance of developing effective radioprotective strategies, particularly in medical and industrial settings, where radiation exposure is prevalent.

Radiation biology is the study of the effects of ionizing radiation on biological tissues and living organisms. It combines radiation physics and biology. The purpose of this chapter is to introduce the terminology and basic concepts of radiobiology to create a better understanding of the ionizing radiation interactions with a living organism. This chapter firstly describes the different types of radiation, the sources, and the radiation interactions with matter. The basic concepts of radioactivity and its applications are also included. Ionizing radiation causes significant physical and chemical modifications, which eventually lead to biological effects in the exposed tissue or organism. The physical quantities and units needed to describe the radiation are introduced here. Eventually, a broad range of biological effects of the different radiation types are addressed. This chapter concludes with a specific focus on the effects of low doses of radiation.

This chapter is focused on radiobiological aspects at the molecular, cellular, and tissue level which are relevant for the clinical use of ionizing radiation (IR) in cancer therapy. For radiation oncology, it is critical to find a balance, i.e., the therapeutic window, between the probability of tumor control and the probability of side effects caused by radiation injury to the healthy tissues and organs. An overview is given about modern precision radiotherapy (RT) techniques, which allow optimal sparing of healthy tissues. Biological factors determining the width of the therapeutic window are explained. The role of the six typical radiobiological phenomena determining the response of both malignant and normal tissues in the clinic, the 6R’s, which are Reoxygenation, Redistribution, Repopulation, Repair, Radiosensitivity, and Reactivation of the immune system, is discussed. Information is provided on tumor characteristics, for example, tumor type, growth kinetics, hypoxia, aberrant molecular signaling pathways, cancer stem cells and their impact on the response to RT. The role of the tumor microenvironment and microbiota is described and the effects of radiation on the immune system including the abscopal effect phenomenon are outlined. A summary is given on tumor diagnosis, response prediction via biomarkers, genetics, and radiomics, and ways to selectively enhance the RT response in tumors. Furthermore, we describe acute and late normal tissue reactions following exposure to radiation: cellular aspects, tissue kinetics, latency periods, permanent or transient injury, and histopathology. Details are also given on the differential effect on tumor and late responding healthy tissues following fractionated and low dose rate irradiation as well as the effect of whole-body exposure.

In recent years, scientific understanding of the changes radiation makes to the various tissues of the body has vastly increased. Identification of biological markers of radiation exposure and response has become a wide field with an increasing interest across the radiation research community. This chapter introduces the concepts of individual radiosensitivity, radiosusceptibility, and radiodegeneration, which are the key factors to classify radiation responses. Biomarkers are then introduced, and their key characteristics as well as classification are explained, with a particular focus on those biomarkers which have been identified for use in epidemiological studies of radiation risk—as this is a crucial topic of current interest within radiation protection. Brief information on collection of samples is followed by a detailed presentation of predictive assays in use in different settings including clinical applications with responses assessed chiefly in tissue biopsy or blood samples. The sections toward the end of this chapter then discuss the evidence associated with the relationship between age and separately sex, and radiosensitivity, as well as some genetic syndromes associated with radiosensitivity. The final section of this chapter provides a brief summary of how our current knowledge can further support individual, personalized, uses of radiation, particularly in clinical settings.

In this chapter, we address the role of radiation as treatment modality in the context of oncological treatments given to patients. Physical aspects of the use of ionizing radiation (IR)—by either photons, neutrons, or charged (high linear energy transfer) particles—and their clinical application are summarized. Information is also provided regarding the radiobiological rationale of the use of conventional fractionation as well as alternative fractionation schedules using deviating total dose, fraction size, number of fractions, and the overall treatment time. Pro- and contra arguments of hypofractionation are discussed. In particular, the biological rationale and clinical application of Stereotactic Body Radiation Therapy (SBRT) are described. Furthermore, background information is given about FLASH radiotherapy (RT), which is an emerging new radiation method using ultra-high dose rate allowing the healthy, normal tissues and organs to be spared while maintaining the antitumor effect. Spatial fractionation of radiation in tumor therapy, another method that reduces damage to normal tissue is presented. Normal tissue doses could also be minimized by interstitial or intraluminal irradiation, i.e., brachytherapy, and herein an overview is given on the principles of brachytherapy and its clinical application. Furthermore, details are provided regarding the principles, clinical application, and limitations of boron neutron capture therapy (BNCT). Another important key issue in cancer therapy is the combination of RT with other treatment modalities, e.g., chemotherapy, targeted therapy, immunotherapy, hyperthermia, and hormonal therapy. Combination treatments are aimed to selectively enhance the effect of radiation in cancer cells or to trigger the immune system but also to minimize adverse effects on normal cells. The biological rationale of all these combination treatments as well as their application in clinical settings are outlined. To selectively reach high concentrations of radionuclides in tumor tissue, radioembolization is a highly interesting approach. Also, radioligand therapy which enables specific targeting of cancer cells, while causing minimal harm surrounding healthy tissues is presented. A brief overview is provided on how nanotechnology could contribute to the diagnosis and treatment of cancer. Last but not least, risk factors involved in acquiring secondary tumors after RT are discussed.

Various exogeneous and endogenous factors constantly cause damages in the biomolecules within a cell. For example, per day, 10,000–100,000 molecular lesions occur in DNA per cell. The molecule modifications that are formed disturb the structure and function of the affected molecules. The purpose of this chapter is to introduce the damages to biomolecules caused by radiation, the associated repair pathways, and the effect on the cellular function. Special interest lies on the damages induced to DNA, the carrier of the human genome, and the consequence to genomic integrity, cell death, and cell survival. Additionally, related effects regarding inflammation and immunity, epigenetic factors, and omics are discussed. The chapter concludes with an explanation of the molecular factors of cellular hyper-radiosensitivity and induced radiation resistance.

This chapter gives an overview of molecules and mechanisms able to intervene with the biological effects of ionizing radiation (IR), either related to their clinical use in radiotherapy or in the field of radiation protection in case of an accidental exposure to radiation and/or nuclear emergencies. According to the National Cancer Institute, “radiomodifiers” can be classified into (a) radioprotectors (protect molecules and tissues from direct and indirect damage induced by IR) or (b) radiomitigators (reduce and help to repair damage), depending on whether they are administered pre- or post-IR exposure, respectively. Most of them are free radical scavengers and antioxidants (or enhancers of the antioxidant defenses), increase DNA repair mechanisms, have anti-inflammatory properties, and/or prevent cell death. On the other hand, (c) radiosensitizers directly or indirectly enhance DNA damage and ROS production, increasing IR toxicity on tumor cells, thus they are used to increase radiotherapy efficacy in cancer patients. The section “Radionuclides and methods to treat contaminated individuals” describes the medical consequences and treatment modalities of internal contamination by radionuclides. Overall, the chapter discusses the effects of most currently known radiomodifiers, their specific properties, and their mechanisms of action, by emphasizing results obtained in recent preclinical and clinical trials.

Ionising radiation is an important form of treatment for human cancer; however, the side effects associated with oxidative damage caused by radiation compromise its effectiveness. This work aimed to quantify the major bioactive components of freeze-dried kiwifruit (KD) and strawberry (SD) extracts and assess their potential efficacy as radioprotective agents in human blood lymphocytes. Their possible genotoxic and cytotoxic effects were also evaluated. The study was conducted by pre-treating human lymphocytes with KD and SD (50, 400, and 800 µg/mL) before radiation at 2 Gy. The results showed that SD presented a higher antioxidant capacity (12.6 mmol Trolox equivalents/100 g db) and higher values of total phenolic compounds (2435 mg of gallic acid equivalents/100 g db), while KD had the highest vitamin C content (322 mg ascorbic acid/100 g db). Regarding phenolic compounds, pelargonidin-3-glucoside was the most abundant in SD (1439 mg/1000 g db) and quercetin-3-O-galactoside in KD (635 mg/1000 g db). None of the tested concentrations of both fruit extracts showed a genotoxic effect. SD (800 µg/mL) reduced the sister chromatid exchange frequency and mitotic index. The efficacy of KD (400 and 800 µg/mL) in lowering the dicentric chromosome frequency demonstrated its radioprotective activity.

Propolis is a natural bee-produced substance with antimicrobial, anti-inflammatory, and wound-healing properties, containing some components from the leaves, buds and resins of plants. It has been used for centuries for various health benefits. In this manuscript, our group reviewed the radioprotective effect of propolis using PubMed and Embase, and our review was conducted according to the PRISMA statement. Finally, 27 articles were included in this review, which includes the radioprotective effect of propolis from cell-based studies (n = 8), animal models (n = 14), and human trials (n = 5). Results reflected that the dosage forms of propolis extracted in the scientific literature were ethanolic extracts of propolis, a water-soluble derivate of propolis, or capsules. The efficacy of the radioprotective properties from propolis is extracted from the bibliography, as several compounds of this resinous mixture individually or synergistically are possible candidates that have the radioprotective effect. In fact, studies prior to 2011 lacked a comprehensive characterization of propolis due to the variability in active compounds among different batches of propolis and were limited to analytical techniques. Furthermore, in this manuscript, we have selected studies to include primarily propolis types from Brazil, Croatia, Egypt, European countries, and those commercialized in Spain. They all contained ethanolic extract of propolis (EEP) and were influenced by different dosage forms. EEP showed a significant presence of lipophilic bioactive compounds like flavones, flavonols, and flavanones.