The psychological effects of ionizing radiation

This paper presents a case study of eleven men who were exposed to non-background ionizing radiation as active participants in the United States' atmospheric nuclear tests. Each of the subjects has developed a virtually identical complex of debilitating psychiatric symptoms. The content of these symptoms is almost entirely focused upon the health effects of the radiation to which each of the subjects was exposed. This symptom complex appears to comprise a syndrome. The symptom structure and course of this syndrome suggests three hypotheses: The syndrome appears to be a pathological development of the self diagnostic belief (that one has been physically harmed by radiation) into a set of symptoms that elaborate upon and express this belief. The self diagnostic belief develops as a means of resolving any one of the various medical mysteries that an individual can experience subsequent to exposure to radiation. Development of the syndrome is a consequence of exposure to non-background ionizing radiation. The paper discusses the evidence for these hypotheses and suggests future research directions.     

Improvement of antioxidant activity of chitosan by chemical treatment and ionizing radiation

Modification of chitosan (CS) to N-maleoylchitosan (NMCS), N-phthaloylchitosan (NPhCS) and sulfonated-chitosan (SCS) was done using maleic anhydride, phthalic anhydride and chlorosulfonic acid, respectively followed by exposing them to γ-rays at different doses. The molecular weights and structural changes of irradiated chitosan derivatives were determined by GPC, FT-IR and UV-vis spectrophotometer. The molecular weights decreased with increasing irradiation dose. Results revealed that the main polysaccharide structure remained after irradiation. To investigate the enhancement of antioxidant activity of chitosan and its derivatives of different molecular weights, radical mediated lipid peroxidation inhibition, scavenging effect of DPPH radicals, reducing power and ferrous ion chelating activity assays were used. Chitosan derivatives with different molecular weights exhibit antioxidant activity. The lower the molecular weights of chitosan and its derivatives, the higher the antioxidant activity. NMCS possessed high scavenging effect on DPPH radicals compared with NPhCS, SCS and ascorbic acid. The irradiated chitosan and its derivatives could be used as natural antioxidants.     

Use of chemical dosimetry for comparison of ultrasound and ionizing radiation effects on cavitation

A comparison of the effects of ultrasound produced by low- and high-frequency ultrasonic apparatuses upon biological systems is one of the basic problems when studying ultrasound cavitation effects. One possibility for how to compare these effects is the indirect method which uses well-known physical quantities characterizing the interaction of ionizing radiation with matter and which also converts these quantities to one common physical quantity. The comparison was performed with two methods applied to the chemical dosimetry of ionizing radiation. The first method employed a two-component dosimeter which is composed of 50 % chloroform and 50 % re-distilled water (i.e. Taplin dosimeter). The other method used a modified iodide dosimeter prepared from a 0.5 M potassium iodide solution. After irradiation or ultrasound exposure, measurable chemical changes occurred in both dosimeters. The longer the exposure, the greater the chemical changes. These effects are described by the relationship of these changes versus the exposure times in both dosimeters. The UZD 21 ultrasonic disintegrator (with a frequency of 20 kHz, 50 % power output) was used as a low-frequency ultrasound source, and the BTL-07 therapeutic instrument (with a frequency of 1 MHz and intensity of 2 W/cm2) was used as a high-frequency cavitation ultrasound source. For comparison, a 60 Co gamma source was applied (60 Co, gamma energies of 1.17 and 1.33 MeV, activity of 14 PBq). Results of this study have demonstrated that the sonochemical products are generated during exposure in the exposed samples of both dosimeters for all apparatuses used. The amount of these products depends linearly upon the exposure time. The resulting cavitation effects were recalculated to a gray-equivalent dose (the proposed unit is cavitation gray [cavitGy]) based on the sonochemical effects compared to the effects of ionizing radiation from the 60 Co source.     

The influence of chemical inhibitors of DNA repair on the recovery of mammalian cell damages induced by ionizing radiation

Using experimental results published by other authors the irreversible component of radiation damage and recovery constant, characterized the probability of recovery of mammalian cells of various origin from radiation damages per unit time, have been calculated. It was shown that the inhibition of postirradiation recovery, displayed in the decreasing of both the rate and the volume of recovery, has occurred due to the increasing in the portion of radiation damages from which the cell is incapable to recover. At the same time the recovery constant was independent on the conditions of combined action in the most cases, being decreasing in small extent only for hydroxyurea and 3-aminobenzamide. It was concluded that the inhibition of recovery is not the main reason of chemical radiosensibilization, but is a quite expected consequence of the increase in the portion of irreversibly damaged cells.     

The effects of ionizing radiation on osteoblast-like cells in vitro

The well-described detrimental effects of ionizing radiation on the regeneration of bone within a fracture site include decreased osteocyte number, suppressed osteoblast activity, and diminished vascularity. However, the biologic mechanisms underlying osteoradionecrosis and the impaired fracture healing of irradiated bone remain undefined. Ionizing radiation may decrease successful osseous repair by altering cytokine expression profiles resulting from or leading to a change in the osteoblastic differentiation state. These changes may, in turn, cause alterations in osteoblast proliferation and extracellular matrix formation. The purpose of this study was to investigate the effects of ionizing radiation on the proliferation, maturation, and cytokine production of MC3T3-E1 osteoblast-like cells in vitro. Specifically, the authors examined the effects of varying doses of ionizing radiation (0, 40, 400, and 800 cGy) on the expression of transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and alkaline phosphatase. In addition, the authors studied the effects of ionizing radiation on MC3T3-E1 cellular proliferation and the ability of conditioned media obtained from control and irradiated cells to regulate the proliferation of bovine aortic endothelial cells. Finally, the authors evaluated the effects of adenovirus-mediated TGF-beta1 gene therapy in an effort to "rescue" irradiated osteoblasts. The exposure of osteoblast-like cells to ionizing radiation resulted in dose-dependent decreases in cellular proliferation and promoted cellular differentiation (i.e., increased alkaline phosphatase production). Additionally, ionizing radiation caused dose-dependent decreases in total TGF-beta1 and VEGF protein production. Decreases in total TGF-beta1 production were due to a decrease in TGF-beta1 production per cell. In contrast, decreased total VEGF production was secondary to decreases in cellular proliferation, because the cellular production of VEGF by irradiated osteoblasts was moderately increased when VEGF production was corrected for cell number. Additionally, in contrast to control cells (i.e., nonirradiated), conditioned media obtained from irradiated osteoblasts failed to stimulate the proliferation of bovine aortic endothelial cells. Finally, transfection of control and irradiated cells with a replication-deficient TGF-beta1 adenovirus before irradiation resulted in an increase in cellular production of TGF-beta1 protein and VEGF. Interestingly, this intervention did not alter the effects of irradiation on cellular proliferation, which implies that alterations in TGF-beta1 expression do not underlie the deficiencies noted in cellular proliferation. The authors hypothesize that ionizing radiation-induced alterations in the cytokine profiles and differentiation states of osteoblasts may provide insights into the cellular mechanisms underlying osteoradionecrosis and impaired fracture healing.     

Membrane effects of ionizing radiation and hyperthermia

Results of numerous studies demonstrate that membranes are important sites of cell damage by both ionizing radiation and hyperthermia. Modification of membrane properties (mainly lipid fluidity) affects the cellular responses to radiation and hyperthermia but former concepts that membrane rigidification sensitizes cells to radiation while membrane fluidization potentiates hyperthermic damage have now been seriously challenged. It seems that the effects of membrane fluidity on cell responses to hyperthermia and radiation are due to an indirect influence on functional membrane proteins. The major role of lipid peroxidation in radiation damage to membranes has also been questioned. The existing evidence makes it unlikely that the interaction between radiation and hyperthermia is determined by the action of both agents on the same membrane components.     

Cellular responses to ionizing radiation: effects of interrupting DNA repair with chemical agents

This review is concerned with the influence of different classes of chemical agents on cellular repair of DNA damage induced by ionizing radiation. Single-strand break rejoining is little affected by inhibitors of DNA synthesis; however, such inhibitors do lead to a persistence of double-strand breaks in the DNA, and this correlates with an enhancement of chromosome aberrations and cell killing. Experiments with antagonists of topoisomerase II suggest an intriguing role for this DNA unwinding enzyme in double-strand break repair. Interference with poly(ADP-ribose) synthesis, by means of the inhibitor 3-aminobenzamide, does not have a clear-cut effect on recovery from ionizing radiation damage. Various substances (for example, caffeine and trypsin) affect DNA repair via a modulation of the cell cycle, altering the time available to the cell for repairing potentially lethal DNA damage before such damage is 'fixed' by the process of DNA replication. Finally, disturbing cellular energy metabolism, and depressing the level of ATP, can inhibit the repair of radiation damage.     

The effects of ionizing radiation on cell cycle progression in ataxia telangiectasia

Although ataxia telangiectasia (AT) cells are more sensitive than normal cells to killing by ionizing radiation, their DNA synthesis is more resistant to inhibition by radiation. It was thought that this anomaly in DNA synthesis was likely to perturb cell cycle progression. Flow cytometry and the fraction of labelled mitoses (FLM) were used to investigate effects of irradiation in normal and AT cell lines. The FLM indicated that radiation apparently induced a longer G2 delay in normal cells than in AT cells. However, flow cytometry showed that radiation induced much larger and more prolonged increases in the proportion of G2 cells in AT than in normals. AT populations also showed much larger postirradiation decreases in viable cell numbers. These data suggest that a large proportion of the radiosensitive AT cells are not reversibly blocked in G2 but die there, and never proceed through mitosis. The less radiosensitive normal cells are delayed in G2 and then proceed through mitosis. We suggest that the apparently shorter radiation-induced mitotic delay seen in AT cells by FLM is not real but is an artifact arising from perturbation of steady state conditions by selective elimination of a particular cohort of AT cells. Accumulation of AT cells in G2 is compatible with radiosensitivity of these cells and may arise from a defect in DNA repair or an anomaly in DNA replication.     

Untargeted effects of ionizing radiation: implications for radiation pathology

The dogma that genetic alterations are restricted to directly irradiated cells has been challenged by observations in which effects of ionizing radiation, characteristically associated with the consequences of energy deposition in the cell nucleus, arise in non-irradiated cells. These, so called, untargeted effects are demonstrated in cells that have received damaging signals produced by irradiated cells (radiation-induced bystander effects) or that are the descendants of irradiated cells (radiation-induced genomic instability). Radiation-induced genomic instability is characterized by a number of delayed adverse responses including chromosomal abnormalities, gene mutations and cell death. Similar effects, as well as responses that may be regarded as protective, have been attributed to bystander mechanisms. Whilst the majority of studies to date have used in vitro systems, some adverse non-targeted effects have been demonstrated in vivo. However, at least for haemopoietic tissues, radiation-induced genomic instability in vivo may not necessarily be a reflection of genomically unstable cells. Rather the damage may reflect responses to ongoing production of damaging signals; i.e. bystander responses, but not in the sense used to describe the rapidly induced effects resulting from direct interaction of irradiated and non-irradiated cells. The findings are consistent with a delayed and long-lived tissue reaction to radiation injury characteristic of an inflammatory response with the potential for persisting bystander-mediated damage. An important implication of the findings is that contrary to conventional radiobiological dogma and interpretation of epidemiologically-based risk estimates, ionizing radiation may contribute to malignancy and particularly childhood leukaemia by promoting initiated cells rather than being the initiating agent. Untargeted mechanisms may also contribute to other pathological consequences.     

The effects of low doses of low-intensity ionizing radiation on DNA structure and function

Chronic effects of low doses of low-intensity ionizing radiation (IR) on biological objects have gained great social significance. This has given a considerable impetus to research into the biological effects and mechanisms of such exposures, both in Russia and abroad. In this paper, an overview of the physicochemical and molecular basis of IR influence at low doses is provided. Means of cell protection from radiation damage are studied and an analysis of the typical features and differences in the radiation effects at low and high doses is carried out. We considered DNA radiation damage, both in cell cultures and in vivo, as well as the processes and results of their repair. Particular attention is paid to changes in the basic paradigms of biological radiation effects at low doses.     

Non-targeted bystander effects induced by ionizing radiation

Radiation-induced bystander effects refer to those responses occurring in cells that were not subject to energy deposition events following ionizing radiation. These bystander cells may have been neighbors of irradiated cells, or physically separated but subject to soluble secreted signals from irradiated cells. Bystander effects have been observed in vitro and in vivo and for various radiation qualities. In tribute to an old friend and colleague, Anthony V. Carrano, who would have said "well what are the critical questions that should be addressed, and so what?", we review the evidence for non-targeted radiation-induced bystander effects with emphasis on prevailing questions in this rapidly developing research field, and the potential significance of bystander effects in evaluating the detrimental health effects of radiation exposure.