Brain proteome response following whole body exposure of mice to mobile phone or wireless DECT base radiation

The objective of this study was to investigate the effects of two sources of electromagnetic fields (EMFs) on the proteome of cerebellum, hippocampus, and frontal lobe in Balb/c mice following long-term whole body irradiation. Three equally divided groups of animals (6 animals/group) were used; the first group was exposed to a typical mobile phone, at a SAR level range of 0.17–0.37 W/kg for 3 h daily for 8 months, the second group was exposed to a wireless DECT base (Digital Enhanced Cordless Telecommunications/Telephone) at a SAR level range of 0.012–0.028 W/kg for 8 h/day also for 8 months and the third group comprised the sham-exposed animals. Comparative proteomics analysis revealed that long-term irradiation from both EMF sources altered significantly (p < 0.05) the expression of 143 proteins in total (as low as 0.003 fold downregulation up to 114 fold overexpression). Several neural function related proteins (i.e., Glial Fibrillary Acidic Protein (GFAP), Alpha-synuclein, Glia Maturation Factor beta (GMF), and apolipoprotein E (apoE)), heat shock proteins, and cytoskeletal proteins (i.e., Neurofilaments and tropomodulin) are included in this list as well as proteins of the brain metabolism (i.e., Aspartate aminotransferase, Glutamate dehydrogenase) to nearly all brain regions studied. Western blot analysis on selected proteins confirmed the proteomics data. The observed protein expression changes may be related to brain plasticity alterations, indicative of oxidative stress in the nervous system or involved in apoptosis and might potentially explain human health hazards reported so far, such as headaches, sleep disturbance, fatigue, memory deficits, and brain tumor long-term induction under similar exposure conditions.     

Control of the G2/M checkpoints after exposure to low doses of ionising radiation: Implications for hyper-radiosensitivity

Two molecularly distinct G2/M cell cycle arrests are induced after exposure to ionising radiation (IR) depending on the cell cycle compartment in which the cells are irradiated. The aims of this study were to determine whether there are threshold doses for their activation and investigate the molecular pathways and possible links between the G2 to M transition and hyper-radiosensitivity (HRS). Two human glioblastoma cell lines (T98G–HRS⁺ and U373–HRS^?) unsynchronized or enriched in G2 were irradiated and flow cytometry with BrdU or histone H3 phosphorylation analysis used to assess cell cycle progression and a clonogenic assay to measure radiation survival. The involvement of ATM, Wee1 and PARP was studied using chemical inhibitors. We found that cells irradiated in either the G1 or S phase of the cell cycle transiently accumulate in G2 in a dose-dependent manner after exposure to doses as low as 0.2 Gy. Only Wee1 inhibition reduced this G2 accumulation. A block of the G2 to M transition was found after irradiation in G2 but occurs only above a threshold dose, which is cell line dependent, and requires ATM activity after exposure to doses above 0.5 Gy. A failure to activate this early G2/M checkpoint correlates with low dose radiosensitization. These results provide evidence that after exposure to low doses of IR two distinct G2/M checkpoints are activated, each in a dose-dependent manner, with distinct threshold doses and involving different damage signalling pathways and confirm links between the early G2/M checkpoint and hyper-radiosensitivity.     

Increased resistance to Listeria monocytogenes following subchronic cyclophosphamide exposure: Relationship to altered bone marrow function

Mice administered multiple doses of cyclophosphamide demonstrated a marked resistance to infection with the bacterium, Listeria monocytogenes. In contrast, acute exposure rendered mice more susceptible to infection than untreated controls. Resistance to infection with Listeria, a facultative intracellular organism, is thought to be dependent upon normal antimicrobial activity early after infection and subsequently through generation of primed T cells. Examination of various macrophage and immune functions, however, failed to demonstrate a significant difference between the two cyclophosphamide-treated groups although both groups were immunosuppressed when compared to untreated controls. Adoptive transfer studies into X-irradiated recipients revealed that repopulation with bone marrow cells from subchronic but not acute cyclophosphamide-treated mice, restored resistance. Furthermore, the numbers of granulocyte/macrophage progenitor cells in the bone marrow were elevated in subchronically treated mice but not acute or unexposed controls. These data suggest the selection of a granulocyte/macrophage progenitor cell possessing a high degree of antilisterial activity following subchronic cyclophosphamide treatment. The effects induced by this exposure regimen are probably related to the enrichment of this cell population resulting from the cell cycle stage specific activity of the drug.     

Principles of the maximum development of the reserve potentialities of the bone marrow CFUf system following exposure to ionizing radiation

In this work, the regularities in the occurrence of a highly pronounced postirradiation increase in CFUf of bone marrow (CFUf "peak") were investigated and quantitative approaches permitting to predict absolute CFUf "peak" values at various radiation doses developed.     

Magnetic resonance imaging using a clinical whole body system: an introduction to a useful technique in small animal experiments.

A clinical whole body magnetic resonance imaging (MRI) system with high resolution coils was used to obtain non-invasive images of the living rat. The results demonstrate the feasibility of the set-up and the advantages of this new imaging technique: detailed information, no extra costs, longitudinal studies without killing animals and simple anaesthesia. It is concluded that in small animal experimentation, this use of high resolution coils in whole body magnetic resonance systems may be particularly helpful in establishing effects of experimental procedures. Whenever non-invasive visualization is required, especially in longitudinal animal studies, e.g. biomaterial research or tumour investigation, this use of MRI will offer challenging possibilities.     

mFISH analysis of chromosomal damage in bone marrow cells collected from CBA/CaJ mice following whole body exposure to heavy ions (<Superscript>56</Superscript>Fe ions)

To date, there is scant information on in vivo induction of chromosomal damage by heavy ions found in space (i.e. ⁵⁶Fe ions). For radiation-induced response to be useful for risk assessment, it must be established in in vivo systems especially in cells that are known to be at risk for health problems associated with radiation exposure (such as hematopoietic cells, the known target tissue for radiation-induced leukemia). In this study, the whole genome multicolor fluorescence in situ hybridization (mFISH) technique was used to examine the in vivo induction of chromosomal damage in hematopoietic tissues, i.e. bone marrow cells. These cells were collected from CBA/CaJ mice at day 7 following whole-body exposure to different doses of 1 GeV/amu ⁵⁶Fe ions (0, 0.1, 0.5 and 1.0 Gy) or ¹³⁷Cs γ rays as the reference radiation (0, 0.5, 1.0 and 3.0 Gy, at the dose rate of 0.72 Gy/min using a GammaCell40). These radiation doses were the average total-body doses. For each radiation type, there were four mice per dose. Several types of aberrations in bone marrow cells collected from mice exposed to either type of radiation were found. These were exchanges and breaks (both chromatid- and chromosome-types). Chromosomal exchanges included translocations (Robertsonian or centric fusion, reciprocal and incomplete types), and dicentrics. No evidence of a non-random involvement of specific chromosomes in any type of aberrations observed in mice exposed to ⁵⁶Fe ions or ¹³⁷Cs γ rays was found. At the radiation dose range used in our in vivo study, the majority of exchanges were simple. Complex exchanges were detected in bone marrow cells collected from mice exposed to 1 Gy of ⁵⁶Fe ions or 3 Gy of ¹³⁷Cs γ rays only, but their frequencies were low. Overall, our in vivo data indicate that the frequency of complex chromosome exchanges was not significantly different between bone marrow cells collected from mice exposed to ⁵⁶Fe ions or ¹³⁷Cs γ rays. Each type of radiation induced significant dose-dependent increases (ANOVA, P < 0.01) in the frequencies of chromosomal damage, including the numbers of abnormal cells. Based upon the linear-terms of dose-response curves, ⁵⁶Fe ions were 1.6 (all types of exchanges), 4.3 (abnormal cells) and 4.2 (breaks, both chromatid- and chromosome-types) times more effective than ¹³⁷Cs γ rays in inducing chromosomal damage.     

Modeling radiation dose and effects from internal emitters in nuclear medicine: from the whole body to individual cells.

In nuclear medicine, proper application of radiation protection principles depends on balancing the potential risks of exposure to ionizing radiation against its possible benefits. Average doses to organs, in diagnostic or therapeutic applications, are not always representative of the doses received at the tissue or cellular level. Therefore, understanding of the relationship between the overall biological effect and absorbed dose delivered by the radiopharmaceutical may require study of doses at the organ, tissue, or cell level. In this paper, we review current models for radiation dose assessment, with consideration of the different models and assumptions employed for study at all levels of investigation.     

The micronucleus test in rat erythrocytes from bone marrow, spleen and peripheral blood: the response to low doses of ionizing radiation, cyclophosphamide and vincristine determined by flow cytometry

The frequency of micronucleated polychromatic erythrocytes (fMPCE) was determined in samples from bone marrow, spleen and peripheral blood of rats exposed to low doses of X-rays, cyclophosphamide or vincristine. The fMPCE values were lower in the peripheral blood than in bone marrow or spleen. This is due to the elimination of MPCE from the circulating blood, which was confirmed by the results from prolonged exposure of rats to gamma-radiation. When the analysis was restricted to the youngest PCE in peripheral blood, the sensitivity of the assay was considerably improved. This can be reproducibly achieved with the flow cytometric analysis.     

Osteopetrosis in the toothless (t1) rat: presence of osteoclasts but failure to respond to parathyroid extract or to be cured by infusion of spleen or bone marrow cells from normal littermates.

Osteoclast have been observe for the first time in toothless (t1) rats, a mutation with inherits osteopetrosis as an autosomal recessive. The ability of t1 rats to raise the serum calcium concentration after injection of parathyroid extract was severely limited when compared with normal littermates. In addition, osteopetrosis in t1 rats is not cured by radiation and infusion of normal spleen or bone marrow cells from normal littermates, a method know to cure osteopetrosis in mutants of this and other species. This indirect evidence for a reduction in bone resorption as a cause of osteopetrosis in this mutation and the failure of transplanted cells to cure the disease are discussed in relation to the development and function of osteoclasts.