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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.

A fundamental possibility of using the ability of low-molecular-weight DNA molecules to form optically active cholesteric liquid-crystalline dispersions (CLCDs) to estimate the efficacy of DNA-binding radioprotectors is studied. On the example of the well-known dye Hoechst 33 258, which interacts with DNA by the minor-groove-binding and has pronounced radioprotective properties, it is shown that the change in the amplitude of anomalous signal of circular dichroism of the CLCDs formed from DNA molecules preliminarily irradiated with X-rays in the absence and in the presence of the test compound makes it possible to estimate the value of its protective effect. [ABSTRACT FROM AUTHOR]

Introduction. The use of radiopharmaceuticals for targeted radionuclide therapy (TRT), the efficacy of which was established during clinical trials, is safe and effective for various pathological conditions, including cancer. The main feature of therapeutic radiopharmaceuticals (RPs) is the use of β–- and α-emitting radionuclides (RNs) in the finished dosage form (FD). Among the radionuclides used for radionuclide therapy, lutetium-177 is currently one of the most popular in clinical practice because of its chemical and nuclear characteristics. The list of RPs based on lutetium-177 is constantly expanding, and Lutathera® ([177Lu]Lu-DOTA-TATE) and Pluvicto™ ([177Lu]Lu-PSMA-617) have been approved for clinical use in several countries.Text. Because of the high activity of RNs in a single dose of therapeutic RPs (up to 8 GBq in a monodose for 177Lu), ionizing radiation of the used RNs leads to a decrease in RPs quality owing to radiolytic degradation of the vector molecule. This leads to a decreased specific accumulation of radioactivity in the foci of pathology, reduced therapeutic effect, and potentially increases the risk of radiotoxicity to non-target organs and tissues. The degree and intensity of radiolytic degradation of the vector molecule and, consequently, the shelf life of RPs depend on many factors, among which the activity concentration of the radionuclide in the preparation, its half-life, and the energy of the emitted particles are the most important. To suppress the effects of radiolysis, various excipients with antioxidant (radioprotective) properties were introduced into the compositions of the finished dosage forms. Among the substances studied, the most popular were gentisic acid, ascorbic acid, and ethanol. In this work, the advantages and disadvantages of various antioxidants and their combinations used in therapeutic RPs were considered in lutetium-177 preparations.Conclusion. Selection of the optimal composition of the dosage form is an urgent task, as it will ensure high-quality RPs both at the time of preparation and during the shelf life and delivery to the end user, which will greatly facilitate the use and centralized supply of therapeutic RPs. The necessity of creating a unified approach for the selection of antioxidants at the pharmaceutical development stage of radiopharmaceuticals is shown. For this purpose, an approach combining studies of radical reaction kinetics with studies of radiation-chemical yields of radiolysis products under identical or maximally similar conditions with subsequent verification of the stability of RPs dosage form seems to be very promising and has proven to be effective. In contrast, the empirical approach, which implies the selection of radioprotectors based on a direct study of their influence on the preservation of the level of radiochemical purity, is suboptimal because of the high market value of both radionuclides and non-radioactive precursors.

Radiation is an important and dangerous factor in contemporary reality in some regions of industrial countries, after technological accidents at nuclear objects, chemical enterprises, etc. This is also the reality of some contemporary military activities and armed conflicts. Radiation damages of organisms can arise also due to the natural reasons — aviation or space flights at high altitudes or even long stay on mountain heights. Natural reasons of such effects have been studied insufficiently for today. Purpose. To outline briefly some results of studies of the characteristics of ionizing radiation at different heights above the Earth. To describe briefly the influence of radiation factors on biological organisms and main mechanisms of these effects. To describe effects that cause pathological changes in organisms of people exposed to the low doses of radiation for a long time and methods of post-radiation rehabilitation of affected people in highlands conditions. Methods. Space satellite exploring of the Earth atmosphere at different altitudes above sea level with measurements of different characteristics of solar and galactic radiation (mainly X-ray, gamma radiation, as well as other types of ionizing radiation in some other ranges). Comparative analysis of the results of longterm observation of patients in hospital conditions using many standard laboratory methods of their states examinations. The conducted scientific research consisted of a complex of methodological techniques and approaches: clinical and physiological studies of respiratory and cardiovascular systems, hematological and immunological states, and functional state of higher nervous activity, mental and neurotic state; administration of antihypoxants, histochemical, biophysical and other methods were used to evaluate oxybiotic processes. Mathematical processing of the results, as well as methods of mathematical modeling was applied. Results. The results of the measurements of ionizing radiation levels during the satellite exploring of the Earth atmosphere at different altitudes were analyzed and presented in schemes. The mechanisms of damaging radiation effects in organisms at nano level were described: water radiolysis, “oxygen effect” as radio sensitizer, formation of various types of free radicals and peroxides with future consequences for organic compounds, cells, tissues, organs, and organisms. The results of medical treatment and rehabilitation at the EMBS of the persons irradiated by the low doses of radiation were presented, observed and discussed. Many of represented results were obtained thanks to the collective work of the great commands of our predecessors in science who searched for the possibilities of medical treatment and rehabilitation of patients who obtained low doses of radiation during long time. The contemporary results of possibilities of some developed pathological states pharmacological corrections were discussed; practical recommendations were done. Conclusions. Some of results of fulfilled works, which can be valuable in the treatment and rehabilitation of people of various contingents exposed to low doses of radiation of various natures for a long time, were presented. The outlined recommendations can be offered to persons of various radiation risk contingents for the purposes of their rehabilitation, in practice of health care, etc.

In the modern world, such a situation has developed that the development of nuclear energy and the use of sources of ionizing radiation in various fields of activity have created a potential threat of radiation hazard to humans. In this connection, the actual direction is the study of ways to increase the radioresistance of human cells and tissues to the action of ionizing radiation. In addition, radioprotective compounds are also important in radiotherapy, since normal tissues of patients must be protected from radiation damage when using high doses of radiation in the treatment of malignant neoplasms. However, the radioprotectors currently used have some disadvantages. The aim of this work is to study the radioprotective properties of fumaric acid and 3-hydroxypyridine fumarate under the action of gamma radiation and radiation of 12C ions on tumor (SK-N-BE neuroblastoma) and normal (hTERT fibroblasts) human cells. The effect of radiation was evaluated according to the criteria of cell survival in culture, doubling time and clonogenic activity. It has been shown that the use of fumaric acid and 3-hydroxypyridine fumarate has a radioprotective effect on normal and tumor cells when they are irradiated with gamma radiation at doses of 1, 4, 6 and 10 Gy. The use of fumaric acid and 3-hydroxypyridine fumarate does not have a radioprotective effect on tumor cells when they are irradiated with 12C ions. A comparative analysis of the results of the action of the preparations with gamma rays and 12C ions showed a significant dependence of the manifestation of modifying properties on the quality of radiation. The study of cell doubling time showed that the presence of drugs in the control did not increase this indicator. On the contrary, under the action of gamma radiation at a dose of 10 Gy, the preparations reduced the doubling time of fibroblasts by more than two times and the doubling time of neuroblastoma cells by almost 1.5 times. The data obtained indicate that the antioxidant properties of the studied preparations open up new possibilities for modifying the action of ionizing radiation in the treatment of oncological diseases. The use of fumaric acid and 3-hydroxypyridine fumarate will reduce the radiation load on healthy cells, including reducing the effect of secondary products on healthy cells beyond the Bragg peak under the action of carbon ion therapy.

Ionizing radiation (IR) is widely applied in radiotherapy for the treatment of over 50% of cancer patients. IR is also intensively used in medical diagnostics on a daily basis in imaging. Moreover, recent geopolitical events have re-ignited the real threat of the use of nuclear weapons. Medical radiation countermeasures represent one of the effective protection strategies against the effects of IR. The aim of this review was to summarize the most commonly used strategies and procedures in the development of radiation countermeasures and to evaluate the current state of their research, with a focus on those in the clinical trial phase. Clinical trials for this review were selected in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was performed in the clinicaltrials.gov database as of May 2022. Our search returned 263 studies, which were screened and of which 25 were included in the review. 10 of these studies had been completed, 3 with promising results: KMRC011 increased G-CSF, IL-6, and neutrophil counts suggesting potential for the treatment of hematopoietic acute radiation syndrome (H-ARS); GC4419 reduced the number of patients with severe oral mucositis and its duration; the combination of enoxaparin, pentoxifylline, and ursodeoxycholic acid reduced the incidence of focal radiation-induced liver injury. The agents discovered so far show significant side effects or low efficacy, and hence most of the tested agents terminate in the early stages of development. In addition, the low profitability of this type of drug demotivates the private sector to invest in such research. To overcome this problem, there is a need to involve more public resources in funding. Among the technological opportunities, a deeper use of in silico approaches seems to be prospective. [ABSTRACT FROM AUTHOR]

The possibility of penetration of sodium-copper chlorophyllin into lymphocytes was evaluated. For this purpose, the content of chlorophyllin in lysates of lymphocytes preincubated in a medium containing 300 μM of copper chlorophyllin was determined by photometric method. A large intracellular content of chlorophyllin was found, which suggested that it can enter the cells. The question remained unanswered whether chlorophyllin can penetrate the nuclear membrane. Based on the analysis of his own information and presented in the literature, the author came to the conclusion that chlorophyllin passes through it much worse than through the plasmalemma. [ABSTRACT FROM AUTHOR]

For decades, Dr. John Moulder has been a leading radiation biologist and one of the few who consistently supported the study of normal tissue responses to radiation. His meticulous modeling and collaborations across the field have offered a prime example of how research can be taken from the bench to the bedside and back, with the ultimate goal of providing benefit to patients. Much of the focus of John's work was on mitigating damage to the kidney, whether as the result of accidental or deliberate clinical exposures. Following in his footsteps, we offer here a brief overview of work conducted in the field of radiation-induced bladder injury. We then describe our own preclinical experimental studies which originated as a response to reports from a clinical genome-wide association study (GWAS) investigating genomic biomarkers of normal tissue toxicity in prostate cancer patients treated with radiotherapy. In particular, we discuss the use of Renin-Angiotensin System (RAS) inhibitors as modulators of injury, agents championed by the Moulder group, and how RAS inhibitors are associated with a reduction in some measures of toxicity. Using a murine model, along with precise CT-image guided irradiation of the bladder using single and fractionated dosing regimens, we have been able to demonstrate radiation-induced functional injury to the bladder and mitigation of this functional damage by an inhibitor of angiotensin-converting enzyme targeting the RAS, an experimental approach akin to that used by the Moulder group. We consider our scientific trajectory as a bedside-to-bench approach because the observation was made clinically and investigated in a preclinical model; this experimental approach aligns with the exemplary career of Dr. John Moulder. Despite the differences in functional endpoints, recent findings indicate a commonality between bladder late effects and the work in kidney pioneered by Dr. John Moulder. We offer evidence that targeting the RAS pathway may provide a targetable pathway to reducing late bladder toxicity. [ABSTRACT FROM AUTHOR]

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Radiation is an important and dangerous factor in contemporary reality in some regions of industrial countries, after technological accidents at nuclear objects, chemical enterprises, etc. This is also the reality of some contemporary military activities and armed conflicts. Radiation damages of organisms can arise also due to the natural reasons — aviation or space flights at high altitudes or even long stay on mountain heights. Natural reasons of such effects have been studied insufficiently for today. Purpose. To outline briefly some results of studies of the characteristics of ionizing radiation at different heights above the Earth. To describe briefly the influence of radiation factors on biological organisms and main mechanisms of these effects. To describe effects that cause pathological changes in organisms of people exposed to the low doses of radiation for a long time and methods of post-radiation rehabilitation of affected people in highlands conditions. Methods. Space satellite exploring of the Earth atmosphere at different altitudes above sea level with measurements of different characteristics of solar and galactic radiation (mainly X-ray, gamma radiation, as well as other types of ionizing radiation in some other ranges). Comparative analysis of the results of longterm observation of patients in hospital conditions using many standard laboratory methods of their states examinations. The conducted scientific research consisted of a complex of methodological techniques and approaches: clinical and physiological studies of respiratory and cardiovascular systems, hematological and immunological states, and functional state of higher nervous activity, mental and neurotic state; administration of antihypoxants, histochemical, biophysical and other methods were used to evaluate oxybiotic processes. Mathematical processing of the results, as well as methods of mathematical modeling were applied. Results. The results of the measurements of ionizing radiation levels during the satellite exploring of the Earth atmosphere at different altitudes were analyzed and presented in schemes. The mechanisms of damaging radiation effects in organisms at nano level were described: water radiolysis, “oxygen effect” as radio sensitizer, formation of various types of free radicals and peroxides with future consequences for organic compounds, cells, tissues, organs, and organisms. The results of medical treatment and rehabilitation at the EMBS of the persons irradiated by the low doses of radiation were presented, observed and discussed. Many of represented results were obtained thanks to the collective work of the great commands of our predecessors in science who searched for the possibilities of medical treatment and rehabilitation of patients who obtained low doses of radiation during long time. The contemporary results of possibilities of some developed pathological states pharmacological corrections were discussed; practical recommendations were done. Conclusions. Some of results of fulfilled works, which can be valuable in the treatment and rehabilitation of people of various contingents exposed to low doses of radiation of various natures for a long time, were presented. The outlined recommendations can be offered to persons of various radiation risk contingents for the purposes of their rehabilitation, in practice of health care, etc. [ABSTRACT FROM AUTHOR]

Currently, natural plant extracts, which include biologically active substances, are increasingly used to produce medicines and cosmetics. In connection with the dangers of a radioecological crisis, special attention is paid to finding ways to protect against the effects of chronic exposure to low-intensity ionizing radiation in natural conditions. Currently, there is no ideal and safe radioprotective agent available, and we are seeing a great effort to find these agents from natural sources. Poplar extract is possible for use as a radioprotective shield from γ-radiation. Samples of protective screens were made from poplar extract on paper and showed a significant radioprotective effect. Phenolic compounds and flavonoids are widely present in plants as a second metabolite and are considered for research depending on their benefits for human health, healing and preventing many disorders. The main biologically active properties of flavonoids include antioxidant, anti-inflammatory, antitumor, rejuvenating, antibacterial and viral, neuroprotective and radioprotective action. The aim of this work was - the study of Flavonoids in an extract obtained from poplar buds and the possibility of their use for protection against radiation. Materials and methods. The object of research is the vegetative organs of poplar (buds). In the process of work, experimental studies were carried out on the extraction and separation of natural compounds, identification of flavonoids, and study of the chemical composition of biologically active complexes of poplar and preparations based on them. Research results. Data from these studies provide the identification of flavonoids by spectroscopy and quantification of flavonoids in poplar bud extract and can contribute to the optimization of radioprotection procedures. The main components found in the poplar buds dry extract are 2',6'-dihydroxy-4'-methoxychalcone - are 2',6'-dihydroxy-4'-methoxychalcone - 2.67 %, 3,4-dihydro-2',6'-dihydroxy-4'-methoxychalcone - 2.33 %, pinobaxin - 1.91 %, chrysin - 0.76 %, pinostrobin - 0.04 %, pinocembrin - 0.61 %, tectochrysin - 0.54 % and galangin - 0.18 % of dry material. The results showed that the power of the penetrating radiation decreases with increasing the thickness of the protective screen. The power of penetrating radiation decreased from 78 % at the layer of 0.5 mm to 10 % at 3 mm layer thickness. Further increasing the thickness of the protective screen (>3 mm), doesn't affect the dose rate. Conclusions. The composition of the poplar buds' ethanol extract was investigated. Samples of protective screens made on the basis of poplar extract on paper showed a significant radioprotective effect on low-intensity ionizing radiation. [ABSTRACT FROM AUTHOR]

Exposure to ionizing radiation can be accidental or for medical purposes. Analyzes of the frequency of radiation damage in the general population, it has been determined that by far the most common are those that occur as a result of diagnostic or therapeutic procedures. Damage caused by radiation, either accidentally or for therapeutic purposes, can be reduced by the use of radioprotectors, mitigators or other therapeutic agents. A detailed research of the available literature shows that there is little systematized data of potentially radioprotective and/or mitigating effects of drugs from the personal therapy of patients during the application of therapeutic ionizing radiation. The aim of this paper is to present review of compounds, especially personal therapy drugs, that exhibit radioprotective and/or mitigating effects after the application of diagnostic or therapeutic ionizing radiation. Given the widespread use of ionizing radiation for diagnostic and therapeutic purposes, there is a clear need to create a strategy and recommendations of relevant institutions for the use of radioprotectors and mitigators in everyday clinical practice, with individual evaluation of the patient's condition and selection of the compounds that will show the greatest benefit in terms of radioprotection. [ABSTRACT FROM AUTHOR]

The radiation protection strategy with chemical agents has long been based on an antioxidative approach consisting in reducing the number of radical oxygen and nitrogen species responsible for the formation of the radiation-induced (RI) DNA damage, notably the DNA double-strand breaks (DSB), whose subset participates in the RI lethal effect as unrepairable damage. Conversely, a DSB repair-stimulating strategy that may be called the "pro-episkevic" approach (from the ancient Greek episkeve, meaning repair) can be proposed. The pro-episkevic approach directly derives from a mechanistic model based on the RI nucleoshuttling of the ATM protein (RIANS) and contributes to increase the number of DSB managed by NHEJ, the most predominant DSB repair and signaling pathway in mammalians. Here, three radioresistant and three radiosensitive human fibroblast cell lines were pretreated with antioxidative agents (N-acetylcysteine or amifostine) or to two pro-episkevic agents (zoledronate or pravastatin or both (ZOPRA)) before X-ray irradiation. The fate of the RI DSB was analyzed by using γH2AX and pATM immunofluorescence. While amifostine pretreatment appeared to be the most efficient antioxidative process, ZOPRA shows the most powerful radiation protection, suggesting that the pro-episkevic strategy may be an alternative to the antioxidative one. Additional investigations are needed to develop some new drugs that may elicit both antioxidative and pro-episkevic properties and to quantify the radiation protection action of both types of drugs applied concomitantly. [ABSTRACT FROM AUTHOR]

Radiation therapy is used as the primary treatment for cancer. Eighty percent of cancer patients require radiation therapy during treatment or for medical purposes. During treatment, radiation causes various biological defects in the cells. The prevalence of cytotoxicity limits the dose used for effective treatment. This method is designed to strike a balance between removing cancer cells and protecting normal tissues. Unfortunately, effective radiation is unavailable once acute toxicity occurs during clinical radiation therapy. Therefore, a lot of research interest is needed in the discovery of radioprotective drugs to accelerate treatment to reduce this toxicity (i.e., normal tissue toxicity to cancer cell death). Radiation protectors may be chemicals or drugs that minimize the damage caused due to radiation therapy in living organisms. The determination of effective and nontoxic radiation protection is an essential goal for radiation oncologists and basic radiobiologists. However, despite the advantages, many radioprotectors were found to have disadvantages which include cost, less duration, toxicity, and effect on the central nervous system. Therefore in recent years, the focus has been diverted to finding out optimal natural products to act as radioprotectors. Natural radiation protectors are plant compounds that protect normal (noncancerous) cells from damage from radiation therapy. Natural herbal products are nontoxic with proven therapeutic benefits and have long been used to treat various diseases. In conclusion, we find that there are various radiation protectors with different purposes and mechanisms of action.

Carnosic acid (CA) is a phenolic diterpene characterized by its high antioxidant activity; it is used in industrial, cosmetic, and nutritional applications. We evaluated the radioprotective capacity of CA on cells directly exposed to X-rays and non-irradiated cells that received signals from X-ray treated cells (radiation induced bystander effect, RIBE). The genoprotective capacity was studied by in vivo and in vitro micronucleus assays. Radioprotective capacity was evaluated by clonogenic cell survival, MTT, apoptosis and intracellular glutathione assays comparing radiosensitive cells (human prostate epithelium, PNT2) with radioresistant cells (murine metastatic melanoma, B16F10). CA was found to exhibit a genoprotective capacity in cells exposed to radiation (p < 0.001) and in RIBE (p < 0.01). In PNT2 cells, considered as normal cells in our study, CA achieved 97% cell survival after exposure to 20 Gy of X-rays, eliminating 67% of radiation-induced cell death (p < 0.001), decreasing apoptosis (p < 0.001), and increasing the GSH/GSSH ratio (p < 0.01). However, the administration of CA to B16F10 cells decreased cell survival by 32%, increased cell death by 200% (p < 0.001) compared to irradiated cells, and increased cell death by 100% (p < 0.001) in RIBE bystander cells (p < 0.01). Furthermore, it increased apoptosis (p < 0.001) and decreased the GSH/GSSG ratio (p < 0.01), expressing a paradoxical radiosensitizing effect in these cells. Knowing the potential mechanisms of action of substances such as CA could help to create new applications that would protect healthy cells and exclusively damage neoplastic cells, thus presenting a new desirable strategy for cancer patients in need of radiotherapy. [ABSTRACT FROM AUTHOR]

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms. [ABSTRACT FROM AUTHOR]

Radiation therapy is used as the primary treatment for cancer. Eighty percent of cancer patients require radiation therapy during treatment or for medical purposes. During treatment, radiation causes various biological defects in the cells. The prevalence of cytotoxicity limits the dose used for effective treatment. This method is designed to strike a balance between removing cancer cells and protecting normal tissues. Unfortunately, effective radiation is unavailable once acute toxicity occurs during clinical radiation therapy. Therefore, a lot of research interest is needed in the discovery of radioprotective drugs to accelerate treatment to reduce this toxicity (i.e., normal tissue toxicity to cancer cell death). Radiation protectors may be chemicals or drugs that minimize the damage caused due to radiation therapy in living organisms. The determination of effective and nontoxic radiation protection is an essential goal for radiation oncologists and basic radiobiologists. However, despite the advantages, many radioprotectors were found to have disadvantages which include cost, less duration, toxicity, and effect on the central nervous system. Therefore in recent years, the focus has been diverted to finding out optimal natural products to act as radioprotectors. Natural radiation protectors are plant compounds that protect normal (noncancerous) cells from damage from radiation therapy. Natural herbal products are nontoxic with proven therapeutic benefits and have long been used to treat various diseases. In conclusion, we find that there are various radiation protectors with different purposes and mechanisms of action. [ABSTRACT FROM AUTHOR]

To describe the contribution of Margarita Malakyan to the development of radiation biology in Armenia and how her multidisciplinary collaboration with chemists, physicists and biologists around the world led to the development of radioprotectors and radiosensitizers of different origins. Margarita Malakyan was a very active and initiative woman, a radiobiologist, whose hard work and enthusiasm led to the establishment of a very constructive scientific network and to the development of newly synthesized metal compounds. During her short but very productive life, the synthesis, characterization, as well as toxicity and radioprotective studies of different compounds led to the suggestion of a number of metal complexes of Schiff bases as effective radioprotective agents and radiosensitizers. [ABSTRACT FROM AUTHOR]

Benzothiazole 6 and benzoselenazole 7, which are closely related to the bisbenzimidazole radioprotector bisbenzimidazole M2PB 20, were prepared by reaction of a common amide intermediate 13O with Lawesson's and Woolin's reagents, respectively. A simpler tellurazole derivative 19 was prepared using a different synthetic strategy. The DNA binding affinity of the three chalcogenazoles 6, 7, 19 and the parent benzimidazole 20 were assessed by means of spectrophotometric DNA titration experiments using 16-mer oligonucleotides with and without a single binding site. While M2PB 20 shows clear binding to the oligonucleotide containing an AATT binding site, no strong conclusions can be made regarding the interactions of 6, 7 or 19 with DNA, either in the presence, or absence of an AATT binding site. Fluorescence microscopy studies with HeLa cells clearly shows nuclear localisation of M2PB (20); fluorescence is almost exclusively in nuclei. By contrast, for the benzoselenazole 7, fluorescence is excluded from the nuclei. These results suggest that the proposed chalcogen bonding interactions involving S, Se and Te in 6, 7, and 20 are not strong enough to impart the DNA binding behavior which is displayed by corresponding bis-benzimidazoles such as 20. [ABSTRACT FROM AUTHOR]

Any collection of objects of study needs some arrangement, i. e. classification. The existing numerous classifications of anti-radiation agents are built on the basis of their anti&radiation effects of an integrated or differentiat& ed nature. The work presents the chronology of the main classifications of chemical compounds that are able to pro& tect against the short&term and long&term effects of ionizing radiation when they are introduced into the body both before and after exposure. The change of views, trends and paradigms regarding radioprotective compounds is shown. These classifications of anti&radiation medicines include radioprotectors, means of stimulating the radioresistance of the body, means of prevention and suppression of the primary reaction to irradiation, means of prevention and treatment of lesions from exposure to incorporated radionuclides, means of treatment of acute bone mar& row syndrome, means of treatment of local radiation lesions. It is shown that modern concepts of radiation protection are based on fundamentally different «points of application» of groups of radioprotective agents and depend on the stage of radiation damage. [ABSTRACT FROM AUTHOR]

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays). [ABSTRACT FROM AUTHOR]

A bystander effect is biological changes in non-irradiated cells by transmitted signals from irradiated bystander cells, which causes the radiation toxic effects on the adjacent non-irradiated tissues. This phenomenon occurs by agents such as ionizing radiation, ultraviolet radiation (UVR) and chemotherapy. The bystander effect includes biological processes such as damage to DNA, cell death, chromosomal abnormalities, delay and premature mutations and micronuclei production. The most involved genes in creating this phenomenon are cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the nuclear factor of kappa B (NFkB) and Mitogen-Activated Protein Kinases (MAPKs).Radiation generated reactive oxygen species (ROS) can damage DNA, membranes and protein buildings. Studies have shown that Vitamin C, Hesperidin, and melatonin can reduce the number of ROS and have a protective role.Silver nanoparticles (Ag NPs) are the most abundant nanoparticles produced and when they enter cells, they can create DNA damage. Studies have shown that combined treatment with UVR and silver nanoparticles could form γ-H2AX and 8-hydroxy-2′-deoxyguanosine (8-OHdG) synergistically.This article reviews the direct and the bystander effects of UVR on the nuclear DNA, the effect of radioprotectors and Ag NPs on these effects.

The radiation protection strategy with chemical agents has long been based on an antioxidative approach consisting in reducing the number of radical oxygen and nitrogen species responsible for the formation of the radiation-induced (RI) DNA damage, notably the DNA double-strand breaks (DSB), whose subset participates in the RI lethal effect as unrepairable damage. Conversely, a DSB repair-stimulating strategy that may be called the “pro-episkevic” approach (from the ancient Greek episkeve, meaning repair) can be proposed. The pro-episkevic approach directly derives from a mechanistic model based on the RI nucleoshuttling of the ATM protein (RIANS) and contributes to increase the number of DSB managed by NHEJ, the most predominant DSB repair and signaling pathway in mammalians. Here, three radioresistant and three radiosensitive human fibroblast cell lines were pretreated with antioxidative agents (N-acetylcysteine or amifostine) or to two pro-episkevic agents (zoledronate or pravastatin or both (ZOPRA)) before X-ray irradiation. The fate of the RI DSB was analyzed by using γH2AX and pATM immunofluorescence. While amifostine pretreatment appeared to be the most efficient antioxidative process, ZOPRA shows the most powerful radiation protection, suggesting that the pro-episkevic strategy may be an alternative to the antioxidative one. Additional investigations are needed to develop some new drugs that may elicit both antioxidative and pro-episkevic properties and to quantify the radiation protection action of both types of drugs applied concomitantly.

Shell-by-Shell (SbS)-functionalized NPs can be tailor-made by combining a metal oxide NP core of choice with any desired phosphonic acids and amphiphiles as 1st or 2nd ligand shell building blocks. The complementary composition of such highly hierarchical structures makes them interesting candidates for various biomedical applications, as certain active ingredients can be incorporated into the structure. Here, we used TiO 2 and CoFe 2 O 4 NPs as drug delivery tools and coated them with a hexadecylphosphonic acid and with hexadecyl ammonium phenolates (caffeate, p-coumarate, ferulate), that possess anticancer as well as antioxidant properties. These architectures were then incubated in 2D and 3D cell cultures of non-tumorigenic and tumorigenic breast cells and irradiated to study their anticancer effect. It was found that both, the functionalized TiO 2 and CoFe 2 O 4 NPs acted as strong protective agents in non-tumorigenic spheroids. In contrast, the functionalized CoFe 2 O 4 NPs induce a higher damage in irradiated tumor spheroids compared to the functionalized TiO 2 NPs. CoFe 3 O 4 NPs act additionally as radiosensitizing agents to the tumor spheroids. The radio-enhancement of the CoFe 2 O 4 NPs is due to the generation of highly toxic hydroxyl radicals during X-ray irradiation. The irradiation exposed the CoFe 2 O 4 surface, releasing the anticancer drugs into the cytoplasm and making the surface Co 2+ ions accessible. These surface ions catalyze the Fenton reaction. This combination of radiosensitizer and anticancer drug delivery proved to be a very effective nanotherapeutic in 2D and 3D cell cultures of breast cancer cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Carnosic acid (CA) is a phenolic diterpene characterized by its high antioxidant activity; it is used in industrial, cosmetic, and nutritional applications. We evaluated the radioprotective capacity of CA on cells directly exposed to X-rays and non-irradiated cells that received signals from X-ray treated cells (radiation induced bystander effect, RIBE). The genoprotective capacity was studied by in vivo and in vitro micronucleus assays. Radioprotective capacity was evaluated by clonogenic cell survival, MTT, apoptosis and intracellular glutathione assays comparing radiosensitive cells (human prostate epithelium, PNT2) with radioresistant cells (murine metastatic melanoma, B16F10). CA was found to exhibit a genoprotective capacity in cells exposed to radiation (p < 0.001) and in RIBE (p < 0.01). In PNT2 cells, considered as normal cells in our study, CA achieved 97% cell survival after exposure to 20 Gy of X-rays, eliminating 67% of radiation-induced cell death (p < 0.001), decreasing apoptosis (p < 0.001), and increasing the GSH/GSSH ratio (p < 0.01). However, the administration of CA to B16F10 cells decreased cell survival by 32%, increased cell death by 200% (p < 0.001) compared to irradiated cells, and increased cell death by 100% (p < 0.001) in RIBE bystander cells (p < 0.01). Furthermore, it increased apoptosis (p < 0.001) and decreased the GSH/GSSG ratio (p < 0.01), expressing a paradoxical radiosensitizing effect in these cells. Knowing the potential mechanisms of action of substances such as CA could help to create new applications that would protect healthy cells and exclusively damage neoplastic cells, thus presenting a new desirable strategy for cancer patients in need of radiotherapy.

Herein we present the results of studying the effects of different isotopes of magnesium, magnetic 25Mg and nonmagnetic 24Mg, upon the post-radiation recovery of yeast cells, S. cerevisiae, irradiated by short-wave UV light (240 - 260 nm) or ionizing radiation (300 Gy). The recovery process of the cells enriched with the magnetic 25Mg proceeds two times faster than the post-radiation recovery of the cells, enriched with the nonmagnetic 24Mg. After gamma-irradiation, the fraction of the irreversible damages in the cells enriched with 25Mg was 50 - 60 % less than in the cells enriched with 24Mg. Thus, the magnetic isotope effect has been detected, i.e. – the acceleration of post-radiation recovery of the cells by the magnetic isotope’s nuclear spin of magnesium (nuclear spin catalysis). Obtained results demonsrate the fundamental possibility of creating new radioprotectors and radiomitigators based on stable magnetic isotopes.

Atomic and radiological crises can be caused by accidents, military activities, terrorist assaults involving atomic installations, the explosion of nuclear devices, or the utilization of concealed radiation exposure devices. Direct damage is caused when radiation interacts directly with cellular components. Indirect effects are mainly caused by the generation of reactive oxygen species due to radiolysis of water molecules. Acute and persistent oxidative stress associates to radiation-induced biological damages. Biological impacts of atomic radiation exposure can be deterministic (in a period range a posteriori of the event and because of destructive tissue/organ harm) or stochastic (irregular, for example cell mutation related pathologies and heritable infections). Potential countermeasures according to a specific scenario require considering basic issues, e.g., the type of radiation, people directly affected and first responders, range of doses received and whether the exposure or contamination has affected the total body or is partial. This review focuses on available medical countermeasures (radioprotectors, radiomitigators, radionuclide scavengers), biodosimetry (biological and biophysical techniques that can be quantitatively correlated with the magnitude of the radiation dose received), and strategies to implement the response to an accidental radiation exposure. In the case of large-scale atomic or radiological events, the most ideal choice for triage, dose assessment and victim classification, is the utilization of global biodosimetry networks, in combination with the automation of strategies based on modular platforms.

The problem of radiation-induced lesions is becoming increasingly urgent. Studies in recent years show that one of the most vulnerable tissues is the endothelium when exposed to high doses of ionizing radiation. The study of the pathogenetic bases of this phenomenon has shown that damage to endotheliocytes occurs both at the expense of the direct exposure to radiation and due to the systemic disturbance of homeostasis which leads to the disadaptation of the executive and regulatory systems of the organism. In this review we considered the mechanisms of the development of endothelial dysfunction under the influence of radioactive radiation and possible methods of pharmacological correction of this condition.

Radiosensitizers and radioprotectors are the compounds that modify the radiation therapy treatment. Radiosensitizers make tumor cell more sensitive to radiation therapy which increases the effectiveness of cancer treatment, whereas radioprotectors are the compounds that reduce the damage/spare normal tissue. Several of these compounds have been studied using appropriate biological model system and their efficacy is reported in literature. The main objectives of the bioinformatics database is to bring on single platform for researchers and clinicians. Therefore, we have developed bioinformatics database of radiosensitizers and radioprotectors using information available in PubMed, scientific journals, and other scientific sources. The collected information of these compounds systematically organized on single platform where a user can browse typical information of the compound. The information pertaining to these compounds is mainly on structural features, radiobiological aspects, biological targets, clinical trials, pharmacological aspects, toxicity, etc. Hence, the database would help clinicians, researchers, and scientists for the improvement of radiation therapy treatment.

Abstract—The possibilities of improving medical protectors administered by inhalation for urgent assistance in emergency situations are discussed in this paper. The advantages of this method of administration are characterized, and the expediency of using portable dry powder inhalers as a technical means of drug delivery is substantiated. The sources containing information on the inhalation use of drugs from various pharmacological groups has been examined. Radioprotective agents (cystamine, indraline, naphthyzine), radioprotective agents for prophylactic use (estradiol), means of preventing and arresting the primary reaction to radiation (ondansetron, metoclopramide, metacin), radiomitigators (analogs of granulocyte colony stimulating factor (G-CSF), growth hormone, betaleukin), and incorporated binding agents radionuclides (pentacin) should be considered as the most promising medical preparations for inhalation under exposure to radiation factors. This is determined by the presence of effective inhalation forms approved for medical use and registered in the Russian Federation, as well as their technological feasibility. [ABSTRACT FROM AUTHOR]

Ionizing radiation results in extensive damage to biological systems. The massive amount of ionizing radiation from nuclear accidents, radiation therapy (RT), space exploration, and the nuclear battlefield leads to damage to biological systems. Radiation injuries, such as inflammation, fibrosis, and atrophy, are characterized by genomic instability, apoptosis, necrosis, and oncogenic transformation, mediated by the activation or inhibition of specific signaling pathways. Exposure of tumors or normal cells to different doses of ionizing radiation could lead to the generation of free radical species, which can release signal mediators and lead to harmful effects. Although previous FDA-approved agents effectively mitigate radiation-associated toxicities, their use is limited due to their high cellular toxicities. Preclinical and clinical findings reveal that phytochemicals derived from plants that exhibit potent antioxidant activities efficiently target several signaling pathways. This review examined the prospective roles played by some phytochemicals in altering signal pathways associated with radiation response.

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays).

An analysis of the current status and future directions of developing medicines for the prevention and early treatment of radiation damage has been conducted. Among radioprotectors, only B-190 (Indralin) is approved for use in the Russian Federation; the main radioprotector in foreign countries is amifostine (Ethyol). Some prospects in the development of new radioprotectors are associated with inhibitors of NO-synthases from the class of N-acyl-S-alkyl-substituted isothiourea derivatives, among which chemical compounds with a pronounced radioprotective effect are found. A recombinant human interleukin-1β (Betaleukin) has been registered in Russia as a radiomitigator intended for use in the early period after accidental irradiation. The US Food and Drug Administration (FDA) has approved the investigational new drug status for seven radiomitigators, including 5-androstenediol (Neumune), genistein (BIO 300), CBLB502 (Entolimod), a kinase inhibitor ON01210 (Ex-RAD), recombinant human interleukin-12 (HemaMax), beclomethasone (OrbeShield), and a granulocyte colony-stimulating factor (G-CSF, Neupogen). Ondansetron hydrochloride dihydrate (Latran) was registered as an antiemetic drug for prevention and therapy of the primary response to radiation in Russia, and granisetron (Kytril) was registered as an antiemetic drug upon irradiation abroad. Potassium iodide, potassium ferric hexacyanoferrate (Ferrocin), diethylenetriaminepentaacetate calcium trisodium (Pentacin, calcium trisodium pentetate), and 2,3-dimercaptopropansulfonate sodium (Unithiol) are used in Russia for the prevention and treatment of damage from irradiation via incorporated radionuclides. Potassium iodide (ThyroShield), diethylenetriaminepentaacetate zinc trisodium (Zn-DTPA, Pentetate zinc trisodium), diethylenetriaminepentaacetate calcium trisodium (Ca-DTPA, Pentetate calcium trisodium), and ferric hexacyanoferrate (Prussian blue, Radiogardase) are used as decorporation agents abroad. Cytokines, vitamins, low-molecular compounds, inhibitors of apoptosis, etc., are considered promising means for the prevention and early treatment of radiation damage. [ABSTRACT FROM AUTHOR]

Herein we present the results of studying the effects of different isotopes of magnesium, magnetic 25Mg and nonmagnetic 24Mg, upon the post-radiation recovery of yeast cells, S. cerevisiae, irradiated by short-wave UV light (240 -260 nm) or ionizing radiation (300 Gy). The recovery process of the cells enriched with the magnetic 25Mg proceeds two times faster than the post-radiation recovery of the cells, enriched with the nonmagnetic 24Mg. After gamma-irradiation, the fraction of the irreversible damages in the cells enriched with 25Mg was 50 -60 % less than in the cells enriched with 24Mg. Thus, the magnetic isotope effect has been detected, i.e. – the acceleration of post-radiation recovery of the cells by the magnetic isotope’s nuclear spin of magnesium (nuclear spin catalysis). Obtained results demonsrate the fundamental possibility of creating new radioprotectors and radiomitigators based on stable magnetic isotopes. [ABSTRACT FROM AUTHOR]

Hanns Langendorff (1902–1974) was an eminent radiobiologist and a visionary, who not only helped found the field, but also made significant scientific contributions. He was a member of the first editorial board of IJRB and actually published a paper in its first issue about the radio-protector 5-hydroxytryptamine. Langendorff started working in the field of radiobiology in 1929 and became director of the 'Radiologisches Institut' of Freiburg University in 1936. His studies impressively show the development of radiobiology over decades in areas such as radiation-induced cell death at various stages of development, as well as radiosensitivity of sea urchin, yeast and mammals. Using mice, Langendorff made many early discoveries about spermatogenesis, hematopoiesis, prenatal development, chromosomal damage and metabolic pathways after exposures to X-rays and neutrons. He also investigated aspects of target theory and dosimetry and developed personal dosimeters using films. After the atomic bomb catastrophes in Japan, Langendorff and his collaborators soon began research in mice related to acute radiation sickness and stimulated the development of radioprotectors by studying their mechanisms of action associated with cell death, as well as cellular and metabolic changes involved. Langendorff also trained a cadre of young scientists who advanced the field and brought it to its golden age in the seventies and the eighties. Research activities of two of his disciples are reviewed: Ulrich Hagen and the author. Both made significant contributions: Hagen mainly studying DNA-damage and repair in vitro as well in cells and the author investigating metabolic processes, cellular and chromosomal damage, prenatal effects, genomic instability, individual radio-sensitivity and their connections to cancer therapy. [ABSTRACT FROM AUTHOR]

Abstract Unmodified hydrated С 60 fullerene molecules (C 60 UHFM) were shown to reduce the formation ROS in water and 8-oxoguanine in DNA upon ionizing radiation impact. C 60 UHFM efficiently eliminate long-lived protein radicals arising after irradiation. In irradiated mice C 60 UHFM reduce the rate of single/double-strand DNA breaks and amount of chromosomal breaks. The radioprotective activity of C 60 UHFM was estimated by the survival rate of animals; the dose modification factor for animal survival was 1.3. Hematological tests showed that C 60 UHFM injection in mice prior to irradiation results in a decrement of irradiation-induced leucopenia and thrombocytopenia. Histological analysis testified that C 60 UHFM provide significant protection of small intestine tissues in mice against irradiation-induced damage. The obtained data assume that the radioprotective properties of C 60 UHFM are determined by their antioxidant, antiradical and DNA-protective qualities. Thus, it was demonstrated that C 60 UHFM are a novel antioxidant and radioprotective agent capable of substantial reduction of the harmful effects of ionizing radiation. Graphical abstract The work included investigation of the effect of unmodified hydrated С 60 fullerene molecules (C 60 UHFM) on the generation of water radiolysis products, such as hydrogen peroxide and hydroxyl radicals, as well as the capability of fullerene to prevent DNA and protein damage under ionizing radiation, and its radioprotective properties and the mechanisms of antiradiation activity in mice. Unlabelled Image [ABSTRACT FROM AUTHOR]

In radiation oncology, the modulation of the bystander effect is a target both for the destruction of tumor cells and to protect healthy cells. With this objective, we determine whether the radioprotective capacity of rosmarinic acid (RA) can affect the intensity of these effects. Genoprotective capacity was obtained by determining the micronuclei frequencies in in vivo and in vitro assays and the cell survival was determined by the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay) (MTT) assay in three cell lines (PNT2, TRAMPC1 and B16F10), both in direct exposure to X-rays and after the production of radiation-induced bystander effect. The administration of RA in irradiated cells produced a decrease in the frequency of micronuclei both in vivo and in vitro, and an increase in cell survival, as expression of its radioprotective effect (p < 0.001) attributable to its ability to scavenge radio-induced free radicals (ROS). However, RA does not achieve any modification in the animals receiving serum or in the cultures treated with the irradiated medium, which expresses an absence of radioprotective capacity. The results suggest that ROS participates in the formation of signals in directly irradiated cells, but only certain subtypes of ROS, the cytotoxic products of lipid peroxidation, participate in the creation of lesions in recipient cells.

Selenium, a micronutrient and an active constituent of important redox enzymes like glutathione peroxidase (GPx) and thioredoxin reductase (TrxR), has been investigated extensively by researchers all over the world for the last four to five decades. Both inorganic and organic selenium compounds are being evaluated as probable drugs or adjuvants for many viral infections and chronic diseases like cancer. Several clinical trials in cancer patients have confirmed that selenium supplementation helps in recovering from cancer therapy associated side effects and selenium itself does not interfere in cancer therapy. Efforts are on to develop new selenium compounds with anti-cancer properties. These aspects will be discussed in this article.

The development of protective agents against harmful radiations has been a subject of investigation for decades. However, effective (ideal) radioprotectors and radiomitigators remain an unsolved problem. Because ionizing radiation-induced cellular damage is primarily attributed to free radicals, radical scavengers are promising as potential radioprotectors. Early development of such agents focused on thiol synthetic compounds, e.g., amifostine (2-(3-aminopropylamino) ethylsulfanylphosphonic acid), approved as a radioprotector by the Food and Drug Administration (FDA, USA) but for limited clinical indications and not for nonclinical uses. To date, no new chemical entity has been approved by the FDA as a radiation countermeasure for acute radiation syndrome (ARS). All FDA-approved radiation countermeasures (filgrastim, a recombinant DNA form of the naturally occurring granulocyte colony-stimulating factor, G-CSF; pegfilgrastim, a PEGylated form of the recombinant human G-CSF; sargramostim, a recombinant granulocyte macrophage colony-stimulating factor, GM-CSF) are classified as radiomitigators. No radioprotector that can be administered prior to exposure has been approved for ARS. This differentiates radioprotectors (reduce direct damage caused by radiation) and radiomitigators (minimize toxicity even after radiation has been delivered). Molecules under development with the aim of reaching clinical practice and other nonclinical applications are discussed. Assays to evaluate the biological effects of ionizing radiations are also analyzed.

Purpose: The purpose of the paper was to investigate the protective effect of some scavengers of OH radicals (hydroxyl radicals) on the radiation sensitivity of bacteria (in some cases also yeast) under normoxic (in air) or hypoxic (suboxic) conditions and to compare the obtained results with those published earlier for the yeast, all in a wide interval of irradiation conditions. Another aim was to investigate a possible impact of the reaction order of the reaction between the scavengers and the OH radicals on the protection of the cells. Materials and Methods: In order to study the protective effect of OH scavengers we used various concentrations of methanol and potassium formate (in some cases also ethanol) in isotonic salt solutions. These solutions containing living bacteria (Escherichia coli) or yeast (Saccharomyces cerevisiae) were irradiated with 60Co radiation using various doses and dose rates. Irradiation was performed in air, in some cases under the hypoxic conditions. The number of surviving cells was determined prior to and after irradiation in suspension with and without scavengers. The surviving fractions after irradiation with and without scavenger were evaluated. Results: The surviving fraction of bacterial cells increases linearly with increasing concentration of both scavengers. The fraction of surviving cells does not increase with increasing concentration of the scavengers under suboxic conditions. The protective effect Ϭ increases linearly with increasing scavenging efficiency and this dependence is much sharper under normoxic conditions than under suboxic ones. The specific protection k is much higher for the methanol than for the potassium formate. Conclusions: The basic characteristics of the impact of scavengers of OH radicals on radiation sensitivity of both bacteria and yeast are the same in a wide interval of doses and dose rates. The specific protection effect is much higher under the normoxic conditions. This protective effect is inversely proportional to the rate constant of the reaction between the scavenger and the OH radicals. It seems to be obvious that the presence of oxygen during irradiation is a necessary condition for the protective action of the scavengers which may be partially controlled by some transport processes and may be connected with the radiation sensitivity of the cells. On the other hand, the change of the reaction order of the reaction of the scavenger with the OH radicals has turned out to be unimportant. [ABSTRACT FROM AUTHOR]

Cancer is a complex multifaceted illness that affects different patients in discrete ways. For a number of cancers the use of chemotherapy has become standard practice. Chemotherapy is a use of cytostatic drugs to cure cancer. Cytostatic agents not only affect cancer cells but also affect the growth of normal cells; leading to side effects. Because of this, radiotherapy gained importance in treating cancer. Slaughtering of cancerous cells by radiotherapy depends on the radiosensitivity of the tumor cells. Efforts to improve the therapeutic ratio have resulted in the development of compounds that increase the radiosensitivity of tumor cells or protect the normal cells from the effects of radiation. Amifostine is the only chemical radioprotector approved by the US Food and Drug Administration (FDA), but due to its side effect and toxicity, use of this compound was also failed. Hence the use of herbal radioprotectors bearing pharmacological properties is concentrated due to their low toxicity and efficacy. Notably, in silico methods can expedite drug discovery process, to lessen the compounds with unfavorable pharmacological properties at an early stage of drug development. Hence a detailed perspective of these properties, in accordance with their prediction and measurement, are pivotal for a successful identification of radioprotectors by drug discovery process. [ABSTRACT FROM AUTHOR]

Radiotherapy is one of the most efficient ways to treat cancer. However, deleterious effects, such as acute and chronic toxicities that reduce the quality of life, may result. Naturally occurring compounds have been shown to be non-toxic over wide dose ranges and are inexpensive and effective. Additionally, pharmacological strategies have been developed that use radioprotectors to inhibit radiation-induced toxicities. Currently available radioprotectors have several limitations, including toxicity. In this review, we present the mechanisms of proven radioprotectors, ranging from free radical scavenging (the best-known mechanism of radioprotection) to molecular-based radioprotection (e.g., upregulating expression of heat shock proteins). Finally, we discuss naturally occurring compounds with radioprotective properties in the context of these mechanisms. [ABSTRACT FROM AUTHOR]

Abstract: This study presents the results and comparison of the distinctive features of the modifying effect of astaxanthin (20.0 μg/mL) on γ-radiation-induced chromosomal instability in human peripheral blood lymphocytes that were irradiated in vitro (1.0 Gy) at the G0, S, and G2 stages of the cell cycle. The study showed that the effect of astaxanthin on cells irradiated at cell cycle stages S and G2 did not lead to changes in the mean frequencies and the spectrum of radiation-induced chromosomal aberrations (p > 0.05). A powerful protective effect of astaxanthin on the level of radiation-induced chromosomal instability (p < 0.001) was observed only in cells that were irradiated at the G0 stage. Thus, the dependence of the radioprotective effect of astaxanthin on the mitotic cycle stage at which the cells were exposed to radiation was established. [ABSTRACT FROM AUTHOR]