Change in the succinate dehydrogenase activity of peripheral lymphocytes in the rat in early periods following exposure to ionizing radiation

Activity of succinate dehydrogenase (SDH) in peripheral blood lymphocytes of albino mongrel rats was determined during an hour following gamma-irradiation. The highest SDH activity in blood lymphocytes (a 41 per cent increase) was registered 20-30 min following 75 Gy irradiation of the head. With a dose of 20 Gy the SDH response was twice as low. During 1 h following irradiation with a dose of 200 Gy the SDH activity exhibited a 10 per cent decrease.     

Alterations in the rat forebrain apoptosis following exposure to ionizing radiation

Ionizing radiation commonly used in the radiotherapy of brain tumours can cause adverse side effects to surrounding normal brain tissue. The most significant response of adult brain to radiation damage is induction of apoptosis. The adult mammalian subventricular zone (SVZ) of the brain lateral ventricles (LV) and their subsequent lateral ventricular extension, the rostral migratory stream (RMS), is one of the few areas, which retains the ability to generate new neurons and glial cells throughout life. Taking into account the fact, that ionizing radiation is one of the strongest exogenous factors affecting cell proliferation, the aim of the present study was to investigate the occurrence of radiation-induced apoptosis in this neurogenic region. Adult male Wistar rats were investigated 1, 5 or 10 days after single whole-body gamma irradiation with the dose of 3 Gy. Apoptotic cell death was determined by in situ labelling of DNA nick ends (TUNEL) and fluorescence microscopy evaluation of TUNEL-positive cells. Considerable increase of apoptotic TUNEL-positive cells was observed 24 hrs after irradiation in caudal parts of RMS; i.e. in the vertical arm and elbow of RMS. Initial increase was followed by strong reduction of apoptosis in the RMS and by secondary over-accumulation of apoptotic cells in the animals that survived ten days after exposure. Results showed, that the proliferating population of cells, arisen in SVZ are highly sensitive to radiation-induced apoptosis. This observation should have implications for clinical radiotherapy to avoid complications in therapeutic brain irradiation.     

In vivo and in vitro demonstration of reduced myelin synthesis following early postnatal exposure to ionizing radiation in the rat

Irradiation of the immature central nervous system has been demonstrated histopathologically to result in a reduction in the quantity of myelin seen at later developmental ages [S. A. Gilmore, J. Neuropathol. Exp. Neurol. 22, 294-301 (1963). J. A. Beal and J. L. Hall, J. Neuropathol. Exp. Neurol. 33, 128-143 (1974)]. The results from our investigation indicate that this reduction in myelin content can be attributed to a decrease in sulfatide synthesis. Rats received whole-brain irradiation with 0, 500, 1500, 2000, or 2500 rad at 4 days postnatal (dpn). All of the rats exposed to 2000 or 2500 rad and 70% of those exposed to 1500 rad died within 6 to 10 days. At 17 dpn, animals received single intraperitoneal injections of [35S]sodium sulfate. Myelin synthesis, as indexed by the incorporation of sulfate into total lipids and glycolipids, was reduced in a dose-related fashion. To demonstrate a direct effect of ionizing radiation on myelinogenesis, brain cell reaggregate cultures derived from fetal rats were exposed at 12 days in vitro (div) to 0, 250, 500, 1000, or 1500 rad. A dose-related reduction in [35S]sulfate incorporation through 21 div was demonstrated. Reaggregates exposed to 250 or 500 rad but not 1000 or 1500 rad resumed normal myelin synthesis by 28 div. These changes occurred in the absence of histopathological changes, changes in protein content, and changes in the rate of protein synthesis.     

Mediator processes in the brain structures in the late periods after external and combined exposure to ionizing radiation

In experiments with mature Wistar male rats it was shown that X-radiation of 12.9 mCi/kg and the combined effect of X-rays and 131I of 6.5 mCi/kg changed the rate of mediator processes in the structures responsible for the hypothalamic function regulation. At remote times (6 months) following irradiation differences were observed in the discoordination of mediator interrelations associated with the peculiarities of the indirect effect of external and combined irradiation implemented via endocrine mechanism system.     

Effect of adrenaline on the succinate dehydrogenase activity of peripheral blood lymphocytes of rats following exposure to ionizing radiation

In experiments with albino mongrel female rats, the influence of adrenaline on succinate dehydrogenase (SDG) activity in the peripheral blood lymphocytes of irradiated and intact animals has been investigated. Two minutes after the intraperitoneal administration of adrenaline (1 mg/kg) to intact rats SDG activity sharply rises and 3-4 min it drastically falls. In 6 to 8 min the second peak in the enzyme activity is registered. Twenty minutes after irradiation of rats in the cranio-caudal direction with a dose of 75 Gy delivered to head, the reaction to adrenaline, manifested by the rise in SDG activity, is absent.     

Time-course analysis of mouse serum proteome changes following exposure of the skin to ionizing radiation

Radiation-induced lesion outcomes of normal tissues are difficult to predict. In particular, radiotherapy or local exposure to a radioactive source by accident can trigger strong injury to the skin. The finding of biomarkers is of fundamental relevance for the prediction of lesion apparition and its evolution, and for the settlement of therapeutic strategies. In order to study radiation-induced cutaneous lesions, we developed a mouse model in which the dorsal skin was selectively exposed to ionizing radiation (IR). 2-D difference gel electrophoresis (2-D DIGE) coupled with MS was used to investigate proteins altered in expression and/or PTM in serum. Proteome changes were monitored from 1 day to 1 month postirradiation, at a dose of 40 Gy, in this specific model developing reproducible clinical symptoms ranging from erythema to skin ulceration with wound healing. About 60 proteins (including some isoforms and likely post-translational variants), representing 20 different proteins, that exhibited significant and reproducible kinetic expression changes, were identified using MS and database searches. Several proteins, down- or up-regulated from day one, could prove to be good candidates to prognosticate the evolution of a skin lesion such as necrosis. In addition, we observed shifts in pI of several spot trains, revealing potential PTM changes, which could also serve as indicators of irradiation or as predictors of lesion severity.     

Tissue reactions under chronic exposure to ionizing radiation

Reviewed are radiobiological data on the emergence of tissue reactions that may determine the course and outcome of human chronic irradiation. The main mechanisms of the reaction of hemopoietic, immune, reproductive, endocrine, respiratory systems and skin to long-term and fractionated exposure to ionizing radiation are considered. The problem of developing a new approach to threshold dose estimation for chronic exposure effects is discussed.     

Immunocorrective action of tuftsin during exposure to ionizing radiation

The effect of the tetrapeptide tuftcin (Thr-Lys-Pro-Arg) on the humoral immune response in CBA mice exposed to sublethal irradiation in a dose of 450 sGy was studied. The drug was injected intraperitoneally for 5 days before (series I) or after (series II) radiation exposure. It has been shown that taftcin has no protective action but decreases considerably the immune response lowering due to radiation.     

The Rad9 protein enhances survival and promotes DNA repair following exposure to ionizing radiation

Following DNA damage cells initiate cell cycle checkpoints to allow time to repair sustained lesions. Rad9, Rad1, and Hus1 proteins form a toroidal complex, termed the 9-1-1 complex, that is involved in checkpoint signaling. 9-1-1 shares high structural similarity to the DNA replication protein proliferating cell nuclear antigen (PCNA) and 9-1-1 has been shown in vitro to stimulate steps of the repair process known as long patch base excision repair. Using a system that allows conditional repression of the Rad9 protein in human cell culture, we show that Rad9, and by extension, the 9-1-1 complex, enhances cell survival, is required for efficient exit from G2-phase arrest, and stimulates the repair of damaged DNA following ionizing radiation. These data provide in vivo evidence that the human 9-1-1 complex participates in DNA repair in addition to its previously described role in DNA damage sensing.     

Childhood exposure to ionizing radiation to the head and risk of schizophrenia

While the association between exposure to ionizing radiation and cancer is well established, its association with schizophrenia is unclear. The aim of our study was to assess risk of schizophrenia after childhood exposure to ionizing radiation to the head (mean dose: 1.5 Gy). The study population included an exposed group of 10,834 individuals irradiated during childhood for treatment of tinea capitis in the 1950s and two unexposed comparison groups of 5392 siblings and 10,834 subjects derived from the National Population Registry individually matched to the exposed group by age, sex (when possible), country of birth, and year of immigration to Israel. These groups were followed for a median 46 years for diagnosis of schizophrenia updated to December 2002. The Cox proportional hazards model stratified by matched sets was used to compare the risk of schizophrenia between the groups. Based on 1,217,531 person-years of follow-up, 451 cases were identified. No statistically significant association was found between radiation exposure and schizophrenia for the total group (hazard ratio per 1 Gy to the brain: 1.05, 95% confidence interval: 0.93-1.18) or within subgroups of sex, dose categories or latent period. When comparing a subgroup of subjects irradiated under 5 years of age with the matched unexposed group, the estimated hazard ratio reached 1.18 (95% confidence interval: 0.96-1.44; P = 0.1). The results of our analysis do not support an association between exposure to ionizing radiation and risk of schizophrenia. More research on possible effects of early exposure to ionizing radiation on schizophrenia specifically and brain tissue in general is needed.     

Maternal occupational exposure to ionizing radiation and birth defects

So far, only a few studies investigated occupational exposure to ionizing radiation in pregnancy to cause birth defects (BDs). No association between BDs and ionizing radiation, although described for high-dose exposure, could ever be confirmed for employees, or specific job titles. Here, an explorative analysis of a prospective population-based birth cohort used to quantify the prevalence of BDs in infants between 1/2007 and 2/2008 is presented. An active examination of all livebirths by specially trained paediatricians in two defined areas was performed. Additionally, a study-specific questionnaire distributed among all becoming mothers in the surveyed regions included questions on maternal occupational exposure to ionizing radiation within the first trimester of pregnancy. In 3,816 births (including 165 infants with BDs; 4.3%), maternal answers concerning possible exposures to medical and occupational ionizing radiation were available. Relative risk (RR) estimates in mothers surveyed for occupational exposure to ionizing radiation (wearing a radiation dosimeter) and BDs in the offspring were calculated exploratively. A higher prevalence of infants with BDs (n = 4; 13.8%) was documented in newborns of the 29 surveyed mothers compared to that in 3,787 births from unexposed mothers (n = 161; 4.3%), corresponding to a RR of 3.2 (1.2–8.7). Excluding deformations, the RR increased to 4.0 (1.5–10.7). Adjustment for possible confounders did not change the results substantially.     

Possibility of inducing the adaptive response of cells to exposure to ionizing radiation

Mechanisms of induction of the antimutagenic and anticarcinogenic adaptive repair response of cells to the effect of alkylating substances and other genotoxic agents are discussed. The possibility of induction of adaptive repair response of mammalian cells to low-level radiation is suggested.