Effects Of X-irradiation Research Articles

Therapeutic Doses of Antioxidants Inhibit the Growth and Enhance the Effects Chemotherapy and Radiation Therapy on Cancer Cells by Blocking the Uptake and Metabolism of Glucose and Glutamine

Chemotherapy and radiation therapy have produced increased 5-year survival rate in majority of cancers; however, acute side-effects during treatment and late adverse effects after these therapies remain a major concern of oncologists. To improve further 5-year survival rate and reduce acute and late adverse effects of therapies, a new non-toxic biological approach is needed. Experimental data for such an approach was available for over 25 years. For example, therapeutic doses of antioxidants inhibit the growth of cancer cells and enhances the growth-inhibitory effects of chemotherapeutic agents and x-irradiation on cancer cells but not on normal cells. These exciting observations failed to draw any attention from oncologists, because mechanistic data on therapeutic doses was not available until now. The mechanistic data on preventive doses of antioxidants suggested that they scavenge free radicals. Since one of the mechanisms of action of chemotherapy and radiation therapy on cancer cells is mediated by free radicals, oncologists fear that supplementation with antioxidants may reduce the effectiveness of cancer therapies by neutralizing free radicals. Cancer cells require glucose and glutamine for their survival and proliferation. This review briefly describes the effects of therapeutic doses of antioxidants alone and in combination with chemotherapy and radiation therapy on the growth of neoplastic cells and normal cells. It also presents evidence to show that such doses of antioxidants reduce the uptake and metabolism of glucose and glutamine in cancer cells. We propose that therapeutic doses of multiple antioxidants can selectively kill cancer cells and enhance the growth-inhibitory effects of therapeutic agents on cancer cells without affecting normal cells by inhibiting the uptake and metabolism of glucose and glutamine.

Green cocoon-derived sericin reduces cellular damage caused by radiation in human keratinocytes

Radiation therapy used in the treatment of cancer causes skin damage, and no method of care has been established thus far. Recently, it has become clear that sericin derived from silkworm cocoons has moisturizing and antioxidant functions. In addition, green cocoon-derived sericin, which is rich in flavonoids, may have enhanced functions. However, whether this green cocoon-derived sericin can reduce radiotherapy-induced skin damage is unclear. In the present study, we aimed at establishing care methods to reduce skin cell damage caused by X-irradiation using green cocoon-derived sericin. We investigated its effect on human keratinocytes using lactate dehydrogenase activity to indicate damage reduction. Our results showed that green cocoon-derived sericin reduced cell damage caused by X-irradiation. However, this effect was not observed when cells were treated before X-irradiation or with a sericin derived from white cocoons. In addition, green cocoon-derived sericin decreased the levels of reactive oxygen species and lipid peroxidation. Our results suggest that green cocoon sericin mitigates the damaging effect of X-irradiation on cells, hence presenting potential usefulness in reducing skin damage from radiation therapy and opening new avenues in the care of cancer patients.

FTIR spectroscopic investigations of protein conformation provide clues of radioadaptation in the kidney of low-dose irradiated rats

Proteins comprise almost half of the weight of plasma membrane and are responsible for preforming various membrane functions. Functionality of the protein is sensitive to its structure. Therefore, modification of the protein conformation can abrogate its function. We demonstrate the induction of radioadaptation in the kidney of low-dose irradiated rats in the form of diminishing the alterations of the protein secondary structure. The FTIR amide I absorption band fitting using Lorentz function was used to identify the various components of the protein secondary structure. FTIR data show changes in amide I band position, amide I/amide II area ratio, FWHM of amide I band, the shifts in the β-structure bands at 1611, 1623, 1634 cm−1 and the decrease in the β/α ratio. 2Gy x-irradiation lead to an increase in the β-structure at the expense of the α-helix. The effect of 2Gy x-irradiation was diminished when preceded with 100 mGy x-rays 24 h earlier. The data provide clue of induction of radioadaptation in the kidneys of whole-body irradiated rats following receiving a low priming dose 24 h prior to a challenging dose.

The Effect of X-irradiation on the Shelf Life and Proximate Composition of Some Varieties of Tomatoes Commonly Grown in Benue State, Nigeria

Tomato production is a source of income to most rural producers in developing countries like Nigeria. Despite the numerous benefits from this crop, challenges of postharvest losses occasioned by lack of preservation techniques and storage facilities are making its production unprofitable in most developing countries in Africa. This research investigated the effect of X-Irradiation on the shelf life and proximate composition of some varieties of tomatoes commonly grown in Benue State. Five samples each of fully ripe Plum (Lycopersicon esculentum L.-Oval-shaped tomato of Italian origin), Juliet (Lycopersicon esculentum L.-1999 All American Selection Winner), Better Boy (Lycopersicon esculentum L. of USA origin), Giulietta F1 (Lycopersicon esculentum L. – a hybrid from France) and Cherry (Lycopersicon esculentum var. cerasiforme) tomatoes were collected from an experimental farm in Wannune, kilometer 54, Makurdi-Gboko road and exposed to X-irradiation doses of 0.10 mGy, 0.30 mGy, 0.61 mGy, 1.06 mGy and 1.67 mGy using the X-ray machine (Model: 1.2UG13GN) located at Musafaha Imaging Centre Makurdi, Benue State. Results of the investigation revealed that 0.30 mGy and 0.61 mGy are adequate for extension of shelf life of Plum tomatoes by 7 days; 0.30 mGy was effective in extension of shelf life of Juliet and Better Boy tomatoes by 5 and 6 days respectively while 0.61 mGy also proved adequate for extension of shelf life of Giulietta F1 and Cherry tomatoes by 6 and 7 days respectively. Proximate analysis of X-irradiated tomatoes showed no significant changes in the ash, moisture, fat, fibre and carbohydrate contents of all varieties of tomatoes considered (P˃0.05) except the protein contents of Juliet, Better Boy and Giulietta F1 that were significantly affected (P˂0.05). X-irradiation doses in the range of 0.30 mGy – 0.61 mGy are effective for extension of shelf life of tomatoes commonly grown in Benue State.

Modulation of Differentiation and Bone Resorbing Activity of Human (Pre-) Osteoclasts After X-Ray Exposure.

Low-dose radiotherapy (LD-RT) is a local treatment option for patients with chronic degenerative and inflammatory diseases, in particular musculoskeletal diseases. Despite reported analgesic and anti-inflammatory effects, cellular and molecular mechanisms related to osteoimmunological effects are still elusive. Here we test the hypothesis that X-irradiation inhibits the differentiation of precursor osteoclasts into mature osteoclasts (mOC) and their bone resorbing activity. Circulating monocytes from healthy donors were isolated and irradiated after attachment with single or fractionated X-ray doses, comparable to an LD-RT treatment scheme. Then monocytes underwent ex vivo differentiation into OC during cultivation up to 21 days, under conditions mimicking the physiological microenvironment of OC on bone. After irradiation, apoptotic frequencies were low, but the total number of OC precursors and mOC decreased up to the end of the cultivation period. On top, we observed an impairment of terminal differentiation, i.e. a smaller fraction of mOC, reduced resorbing activity on bone, and release of collagen fragments. We further analyzed the effect of X-irradiation on multinucleation, resulting from the fusion of precursor OC, which occurs late during OC differentiation. At 21 days after exposure, the observation of smaller cellular areas and a reduced number of nuclei per mOC suggest an impaired fusion of OC precursors to form mOC. Before, at 14 days, the nuclear translocation of Nuclear Factor Of Activated T Cells 1 (NFATc1), a master regulator of osteoclast differentiation and fusion, was decreased. In first results, obtained in the frame of a longitudinal LD-RT study, we previously reported a pain-relieving effect in patients. However, in a subgroup of patients suffering from Calcaneodynia or Achillodynia, we did not observe a consistent decrease of established blood markers for resorption and formation of bone, or modified T cell subtypes involved in regulating these processes. To assess the relevance of changes in bone metabolism for other diseases treated with LD-RT will be subject of further studies. Taken together, we observed that in vitro X-irradiation of monocytes results in an inhibition of the differentiation into bone-resorbing OC and a concomitant reduction of resorbing activity. The detected reduced NFATc1 signaling could be one underlying mechanism.

Effects of X-Irradiation on the Physicochemical Properties, and the Shelf-Lifeof Four Mango Species in Benue State, Nigeria

Effects of X-Irradiation on the Physicochemical Properties, and the Shelf-Lifeof Four Mango Species in Benue State, Nigeria

RADIATIVE AND MAGNETICALLY STIMULATED CHANGE OF THE ELECTRICAL PROPERTIES OF THE SiO2-Si STRUCTURE WITH A HIGH CONTENT OF DISLOCATION COMPLEXES

The effect of various types of irradiation and magnetic field on the surface of the semiconductor is a relevant topic, since it is the change in the density of the SS that is responsible for the occurrence of sensitive (sensory) effects associated with dislocations adsorbed particles. The paper examines the effect of X-irradiation on the Si surface with different dislocation density (10 2 – 10 5 cm -2 ). The capacitance–voltage characteristics (CVC) of the Bi-SiO 2 -Si-Al structure indicate (their maxima) a sufficiently large charge in the dielectric layer of the capacity of this maximum. As the dislocation density increases, the capacitance value in the region of positive voltages decreases, which is associated with a decrease in the spatial charge region (SCR) value, as well as the distribution of the density of surface states in the band gap and their rate of recharging changes. To determine the density of surface states, the ideal (mathematically calculated) structures of Bi-SiO 2 -Si-Al (MOS) is compared with the real one. It is shown that the maximum concentration of SS is formed in the defect layers of the transition region, in which there are maximum mechanical stresses. The source of such stresses can be dislocations, which contribute to the energy spectrum of the surface. They increase the concentration of surface states in the depicted silicon zone by an order of magnitude. The spectrum becomes more complex with well-defined maxima in the energy range [from -0.1 to +0.4] eV at N ~ 10 5 cm -2 . This is due to the fact that, with low-energy irradiation of barrier structures in silicon oxide, the process of generation of electron-hole pairs occurs. The mobility of electrons in SiO 2 is much higher than the mobility of holes. Electrons that do not recombine leave the dielectric, holes (p + ) thermalize and fall to levels near the ceiling of the valence band. Thermal excitation of holes causes their capture at the level of tight bonds with a disturbance of equilibrium and the movement of atoms from the local to the free energy minimum. At the same time, the reaction takes place: ≡Si-O-Si≡ + p + →Si + +O 0 -Si≡ it shows the formation of "trivalent" silicon and "non-bridging" oxygen, which lead to the emergence of pseudovacancies, which lead to the accumulation of an additional charge in SiO 2 when the silicon structure is irradiated. In this case, the increase in the dislocation density enhances the effect of the radiation-stimulated SS change at the SiO 2 -Si interface. Under the action of X-irradiation on the surface of Si, there is a rearrangement of existing metastable defects and the formation of new ones, the increase in the density of which is associated with heterogeneity them from the volume semiconductor to the surface. They make a significant contribution to the SS spectrum. Upon irradiation, they can reorganize into more complex complexes with a change in SS. As a result of aging the structure Bi-SiO 2 -Si-Al in a magnetic field (MF) (B = 0.17 T) with different dislocation concentrations (terms of 4, 12, 20 days), the SS spectrum changes significantly. At N ≈ 10 4 – 10 5 cm -2 becomes monotonous after 20 days. The effect of a magnetic field on silicon does not cause the generation of electrically active defects in the near-surface layers of semiconductor, but promotes the rearrangement of oxygen and hydrogen complexes adsorbed on the surface, which are present on Si. It is they who determine the nature of the change in the SS due to the actions of the MF. Under the action of a magnetic field, a spin-dependent process of breaking chemical bonds in nanoclusters of structural defects (Si-H, Si-OH, -OH) occurs. As a result of breaking chemical bonds, hydrogen ions diffuse across the crystal and passivate acceptor and donor bonds. In addition, the action of MF leads to dynamic polarization of the nuclei of the Si 29 isotope atom and polarization of the electron spins in Si to the electron spins of oxygen due to the ultrathin interaction with polarized nuclei. A change in the orientation of the electron spin leads to the breakdown of the chemical bond. The effect of MF detection on non-magnetic materials, which are non-magnetic, is enhanced by prolonged exposure of samples to MF and the presence of defects in the near-surface layers. It is obvious that the presence of a dislocation will strengthen the influence of the MF on the change of the SS at the boundary SiO 2 -Si. Key words : silicon, magnetic field, X-irradiation, dislocations.

X- and gamma-irradiation have similar effects on the in vitro quality of stored red cell components.

Blood components are irradiated to inactivate lymphocytes to prevent transfusion-associated graft versus host disease. As there are little data regarding the effects of X-irradiation on red blood cell components (RBCs), the in vitro quality of stored red cells (standard, pediatric, washed, and intra-uterine transfusion [IUT]) following X- or gamma-irradiation was compared. RBCs were pooled, split, and processed to produce standard (<14 days and < 5 days post-collection), pediatric (<5 days post-collection), washed (<14 days post-collection), or IUT RBCs (<5 days post-collection). Standard RBCs were either X- or gamma-irradiated (n=10 pairs). A further 10 replicates were prepared by pooling and splitting three matched RBCs (X-, gamma-, and non-irradiated). All other RBCs were either X- or gamma-irradiated (n=20 pairs). Red cell indices, hemolysis, potassium release, metabolism, microparticles, ATP, and 2,3-DPG were measured pre-irradiation and 6h, 1, 2, 3, 7, 10, and 14 days post-irradiation, depending on the component type. Data were analyzed using two-way repeated measures ANOVA. There were no significant differences in any in vitro quality measurements, with the exception of marginally higher potassium release in washed, IUT, and RBCs <5 days old (p < .0001) following X-irradiation. Both irradiation types increased generation of microvesicles, particularly in components that were older at the time of irradiation or stored for longer post-irradiation. X- and gamma-irradiation have similar effects on the in vitro quality of RBCs, indicating that either technology is suitable for blood component irradiation.

Reduced Tumorigenicity of Mouse ES Cells and the Augmented Anti-Tumor Therapeutic Effects under Parg Deficiency.

PolyADP-ribosylation is a post-translational modification of proteins, and poly(ADP-ribose) (PAR) polymerase (PARP) family proteins synthesize PAR using NAD as a substrate. Poly(ADP-ribose) glycohydrolase (PARG) functions as the main enzyme for the degradation of PAR. In this study, we investigated the effects of Parg deficiency on tumorigenesis and therapeutic efficacy of DNA damaging agents, using mouse ES cell-derived tumor models. To examine the effects of Parg deficiency on tumorigenesis, Parg+/+ and Parg−/− ES cells were subcutaneously injected into nude mice. The results showed that Parg deficiency delays early onset of tumorigenesis from ES cells. All the tumors were phenotypically similar to teratocarcinoma and microscopic findings indicated that differentiation spectrum was similar between the Parg genotypes. The augmented anti-tumor therapeutic effects of X-irradiation were observed under Parg deficiency. These results suggest that Parg deficiency suppresses early stages of tumorigenesis and that Parg inhibition, in combination with DNA damaging agents, may efficiently control tumor growth in particular types of germ cell tumors.

Effects of X-irradiation and sinensetin on apoptosis induction in MDA-MB-231 human breast cancer cells

Effects of X-irradiation and sinensetin on apoptosis induction in MDA-MB-231 human breast cancer cells

X-irradiation of developing hippocampal neurons causes changes in neuron population phenotypes, dendritic morphology and synaptic protein expression in surviving neurons at maturity

The effects of X-irradiation on developing neurons and their functions are unclear. We used primary cultures of mouse hippocampal neurons to investigate the effects of X-irradiation on cell death in developing neurons by analyzing caspase-3, MAP2 and DAPI-labeled cells, and the phenotypes and function of surviving neurons, by examining GAD67-positive cells as a GABAergic marker, and the synaptic markers synapsin 1, drebrin and PSD-95 through its maturation. One-day in vitro (DIV 1) cells were exposed to 0.5 Gy or 1 Gy of X-rays. A significant increase in the percentage of activated caspase-3, a decrease in the number of MAP2/DAPI-positive cells and change in the percentage of GAD67 positive neurons, compared with sham controls, were found 6 days after 1 Gy and 13 days after 0.5 Gy of X-rays. The expression of PSD-95 and drebrin, as well as drebrin clusters, in the remaining neurons was decreased at DIV 21, in both 0.5 Gy and on 1 Gy-irradiation there was a reduced number of dendritic intersection as well. Together, our findings show that 0.5 Gy and 1 Gy of X-irradiation at DIV 1 not only causes neuronal cell death but elicits an increase in the percentage of inhibitory neurons, changes in the dendrites and decrease in expression of important synaptic proteins in the surviving neurons at maturity 3 weeks after exposure.

The effect of X-irradiation on β-glucosidase PYK 10 gene expression in Arabidopsis thaliana (L.) Heynh. seedlings

The effect of X-irradiation on β-glucosidase PYK 10 gene expression in Arabidopsis thaliana (L.) Heynh. seedlings

D,L-Methadone does not improve radio- and chemotherapy in glioblastoma in vitro.

Glioblastoma (GBM) is the most common malignant tumor of the central nervous system. Median survival of glioblastoma patients under standard therapy including radiotherapy and chemotherapy using temozolomide (TMZ) is 14.6 months. As cell culture experiments combining D,L-methadone with doxorubicin demonstrated an increased reduction of cell viability of glioblastoma cells, the opioid has been discussed as a drug for the treatment of GBM. Despite lack of clinical and experimental evidence that D,L-methadone in combination with standard therapy will be beneficial, an increasing number of tumor patients medicating themselves with D,L-methadone present to the hospitals in Germany. As a first step towards understanding whether D,L-methadone may increase the efficacy of standard therapy, we used a cell culture model of primary GBM and fibroblast cell cultures derived from GBM patients. The cultures were treated with different concentrations of D,L-methadone in combination with X-irradiation, TMZ or both. Cell viability was determined by measuring ATP in cell lysates and dehydrogenase activity in living cells. When only treated with D,L-methadone, 1µM of the opioid was sufficient to reduce viability of fibroblasts, whereas 10µM was needed to significantly reduce glioblastoma cell viability. In addition, D,L-methadone did not improve the anti-neoplastic effects of X-irradiation, temozolomide or both. As D,L-methadone reduces glioblastoma cell viability only when concentrations are used that had been reported to be toxic to patients and as there were no interactions observable combining it with standard therapy, a recommendation for the use of D,L-methadone in glioblastoma therapy cannot be given.

MITOCHONDRIAL MEMBRANE POTENTIAL, MORPHOLOGY AND ATP PRODUCTION IN MAMMALIAN CELLS EXPOSED TO X-RAYS.

This study aimed to reveal the effect of X-irradiation on mitochondrial function in terms of mitochondrial membrane potential (ΔΨm) and ATP productivity. At the cellular level, ΔΨm was quantified using JC-1, a mitochondrial probe that emits red or green fluorescence at high or low ΔΨm sites, respectively. The fluorescence area was quantified for both colors together relative to the whole-cell area of the same cell. The fluorescence areas versus whole-cell areas varied widely among the irradiated cells depending on the X-ray doses received (6 and 10 Gy) and incubation time, although the relative red area to total mitochondrial area was rather constant. Average ATP concentrations temporarily increased and showed a maximum at 48 h after irradiation for largely G1-arrested cells. These results indicate that an increase of mitochondrial volume per cell, not simply an increase in their active sites, is induced by irradiation, resulting in enhanced ATP production.

Sulfasalazine, an inhibitor of the cystine-glutamate antiporter, reduces DNA damage repair and enhances radiosensitivity in murine B16F10 melanoma.

The sodium-independent cystine-glutamate antiporter plays an important role in extracellular cystine uptake. It comprises the transmembrane protein, xCT and its chaperone, CD98. Because glutathione is only weakly cell membrane permeable, cellular uptake of its precursor, cystine, is known to be a key step in glutathione synthesis. Moreover, it has been reported that xCT expression affects the progression of tumors and their resistance to therapy. Sulfasalazine is an inhibitor of xCT that is known to increase cellular oxidative stress, giving it anti-tumor potential. Here, we describe a radio-sensitizing effect of sulfasalazine using a B16F10 melanoma model. Sulfasalazine decreased glutathione concentrations and resistance to H2O2 in B16F10 melanoma cells, but not in mouse embryonic fibroblasts. It synergistically enhanced the cyto-killing effect of X-irradiation in B16F10 cells. It inhibited cellular DNA damage repair and prolonged cell cycle arrest after X-irradiation. Furthermore, in an in vivo transplanted melanoma model, sulfasalazine decreased intratumoral glutathione content, leading to enhanced susceptibility to radiation therapy. These results suggest the possibility of using SAS to augment the treatment of radio-resistant cancers.

Impact of X-irradiation on microglia.

Irradiation is widely used to treat brain tumors, and also to create bone marrow (BM) chimeras. BM chimeras are widely used to dissect functions and origin of microglia and blood-derived mononuclear cells under homeostatic or pathological conditions. This is facilitated by the fact that microglia survive irradiation and are thus regarded radio-resistant. In this study, we tested whether microglia are indeed radio-resistant and looked for potential mechanisms that might explain this phenomenon. We analyzed the radio-resistance of microglia independently of their physiological brain environment compared to other mononuclear cells from spleen and brain after X-irradiation with 7 Gy or 30 Gy. Furthermore, we investigated long-term effects of X-irradiation on microglia using organotypic hippocampal slice cultures (OHSCs). We found a significant higher survival rate of isolated microglia 4 hr after X-irradiation with 30 Gy accompanied by a decreased proliferation rate. Investigations of apoptosis-related genes revealed no regulation of a specific antiapoptotic pathway but ataxia telangiectasia mutated (ATM), a DNA-repair-related gene, was significantly upregulated in isolated microglia 4 hr after 30 Gy. Irradiation of OHSCs with 7 and 30 Gy revealed a highly and significantly decreased cell number, morphological changes and an increase in migration velocity of microglia. Furthermore, cell loss, increased soma size and process length of microglia was also found in BM chimeras irradiated with 9.5 Gy 5weeks after irradiation. Here, we present new evidence implying that microglia are not a homogeneous population of radio-resistant cells and report on long-term alterations of microglia that survived irradiation.

Indirect effects of X-irradiation on proliferation and osteogenic potential of bone marrow mesenchymal stem cells in a local irradiated rat model.

Cancer survivors after radiotherapy may suffer a variety of bone-related adverse side effects, including radioactive osteoporosis and fractures. Localized irradiation is a common treatment modality for malignancies. Recently, a series of reactions and injuries called indirect effects (remote changes in bone when other parts of the body are irradiated) have been reported on the indirect irradiated area of bone tissue after radiotherapy. To address this issue, we developed a rat localized irradiation model. Rats were irradiated with a single dose of X-rays to the left hind limbs, and bone marrow mesenchymal stem cells (BMMSCs) were isolated from bone marrow of the left (direct irradiated) and right (indirect irradiated) hind limbs 3, 7 and 14 days after irradiation, and assayed for the proliferation ability and osteogenic potential by alkaline phosphatase (ALP) activity, mineralization assay, RT-PCR and western blot analysis. The results showed that there were significant morphology changes in the BMMSCs from direct and indirect irradiated bone tissue with bigger cell bodies and increased granules. The proliferation of BMMSCs decreased both in the direct irradiated and non-irradiated bone tissue. The ALP expression and activities of BMMSCs from direct irradiated bone was consistently defected following a transient enhancement, the mRNA levels of RUNX2 and OCN, the protein expression of RUNX2, and the mineralization ability also showed the same trend. Simultaneously, in indirect irradiated group, the osteogenic potential indicators of BMMSCs decreased in the early stage of post-irradiation and were still impaired 14 days after irradiation. Our data demonstrate that localized irradiation may have both direct and indirect adverse effects on BMMSCs' proliferation and osteogenic potential into osteoblast, which may be the mechanism of radiation-induced abscopal impairment to the skeleton in the cancer radiotherapy-induced bone loss.

Long-term genotoxic effects in the hematopoietic system of prenatally X-irradiated mice

Purpose: To investigate the genotoxic effects of prenatal X-irradiation in mice and the possible presence of late genomic instability.Materials and methods: Pregnant mice were exposed to 0, 1 or 2 Gy at embryonic day 11.5. Blood smears were obtained from pups at birth and on post-natal day 11, 21, 42 and 140. Hematological data (diameter of erythrocytes, percentage of reticulocytes and Granulocyte-to-Lymphocyte ratio [GLR]) and genotoxicity (micronucleated erythrocytes, micronucleated reticulocytes, CREST-positive and negative micronuclei) were assessed.Results: Prenatal irradiation caused perinatal reticulocytosis (which ended on postnatal day 11) and a dose-dependent increase of GLR (indicative of myeloid skewing) on postnatal days 42 and 140. Two temporally distinct genotoxic effects were observed: an early, acute damage (still detectable at birth and soon after) and a late, long-term damage.Conclusions: Increases in micronuclei frequencies and GLR observed from day 42 on are both ascribable to DNA damage. Time of appearance of this late effect may be linked to the shift of hematopoiesis from spleen to bone marrow and to cell-extrinsic factor such as the microenvironment. This study confirms that ionizing radiation can induce long-term genotoxic effects in the hematopoietic system and shows that prenatal irradiation determines genomic instability in blood-forming tissues of adult mice.

X‐rays effects on cytoskeleton mechanics of healthy and tumor cells

Alterations in the cytoskeleton structure are frequently found in several diseases and particularly in cancer cells. It is also through the alterations of the cytoskeleton structure that cancer cells acquire most of their common features such as uncontrolled cell proliferation, cell death evasion, and the gaining of migratory and invasive characteristics. Although radiation therapies currently represent one of the most effective treatments for patients, the effects of X-irradiation on the cytoskeleton architecture are still poorly understood. In this case we investigated the effects, over time of two different doses of X-ray irradiation, on cell cytoskeletons of BALB/c3T3 and Sv40-transformed BALB/c 3T3 cells (SVT2). Biophysical parameters - focal adhesion size, actin bundles organization, and cell mechanical properties - were measured before and after irradiations (1 and 2 Gy) at 24 and 72 h, comparing the cytoskeleton properties of normal and transformed cells. The differences, before and after X-irradiation, were revealed in terms of cell morphology and deformability. Finally, such parameters were correlated to the alterations of cytoskeleton dynamics by evaluating cell adhesion at the level of focal adhesion and cytoskeleton mechanics. X-irradiation modifies the structure and the activity of cell cytoskeleton in a dose-dependent manner. For transformed cells, radiation sensitively increased cell adhesion, as indicated by paxillin-rich focal adhesion, flat morphology, a well-organized actin cytoskeleton, and intracellular mechanics. On the other hand, for normal fibroblasts IR had negligible effects on cytoskeletal and adhesive protein organization. © 2016 Wiley Periodicals, Inc.

Joseph Altman (1925–2016): A life in neurodevelopment

Joseph Altman (1925–2016): A life in neurodevelopment