137Cs Γ-rays Research Articles

Devastation of adult stem cell pools by irradiation precedes collapse of trabecular bone quality and quantity

Stem cell depletion and compromised bone marrow resulting from radiation exposure fosters long-term deterioration of numerous physiologic systems, with the degradation of the skeletal system ultimately increasing the risk of fractures. To study the interrelationship of damaged bone marrow cell populations with trabecular microarchitecture, 8- and 16-week-old C57BL/6 male mice were sublethally irradiated with 5 Gy of (137)Cs γ-rays, and adult stem cells residing in the bone marrow, as well as bone quantity and quality, were evaluated in the proximal tibia after 2 days, 10 days, and 8 weeks compared with age-matched controls. Total extracted bone marrow cells in the irradiated 8-week, young adult mice, including the hematopoietic cell niches, collapsed by 65% ± 11% after 2 days, remaining at those levels through 10 days, only recovering to age-matched control levels by 8 weeks. As early as 10 days, double-labeled surface was undetectable in the irradiated group, paralleled by a 41% ± 12% and 33% ± 4% decline in bone volume fraction (BV/TV) and trabecular number (Tb.N), respectively, and a 50% ± 10% increase in trabecular separation (Tb.Sp) compared with the age-matched controls, a compromised structure that persisted to 8 weeks postirradiation. Although the overall collapse of the bone marrow population and devastation of bone quality was similar between the "young adult" and "mature" mice, the impact of irradiation--and the speed of recovery--on specific hematopoietic subpopulations was dependent on age, with the older animals slower to restore key progenitor populations. These data indicate that, independent of animal age, complications arising from irradiation extend beyond the collapse of the stem cell population and extend toward damage to key organ systems. It is reasonable to presume that accelerating the recovery of these stem cell pools will enable the prompt repair of the skeletal system and ultimately reduce the susceptibility to fractures.

ERK/GSK3β/Snail signaling mediates radiation-induced alveolar epithelial-to-mesenchymal transition

Radiotherapy is one of the major treatment regimes for thoracic malignancies, but can lead to severe lung complications including pneumonitis and fibrosis. Recent studies suggest that epithelial-to-mesenchymal transition (EMT) plays an important role in tissue injury leading to organ fibrosis. To investigate whether radiation can induce EMT in lung epithelial cells and also to understand the potential mechanism(s) associated with this change, rat alveolar type II lung epithelial RLE-6TN cells were irradiated with 8Gy of 137Cs γ-rays. Western blot and immunofluorescence analyses revealed a time-dependent decrease in E-cadherin with a concomitant increase in α-smooth muscle actin (α-SMA) and vimentin after radiation, suggesting that the epithelial cells acquired a mesenchymal-like morphology. Protein levels and nuclear translocation of Snail, the key inducer of EMT, were significantly elevated in the irradiated cells. Radiation also induced a time-dependent inactivation of glycogen synthase kinase-3β (GSK3β), an endogenous inhibitor of Snail. A marked increase in phosphorylation of ERK1/2, but not JNK or p38, was observed in irradiated RLE-6TN cells. Silencing ERK1/2 using siRNAs and the MEK/ERK inhibitor U0126 attenuated the radiation-induced phosphorylation of GSK3β and altered the protein levels of Snail, α-SMA, and E-cadherin in RLE-6TN cells. Preincubating RLE-6TN cells with N-acetylcysteine, an antioxidant, abolished the radiation-induced phosphorylation of ERK and altered protein levels of Snail, E-cadherin, and α-SMA. These findings reveal, for the first time, that radiation-induced EMT in alveolar type II epithelial cells is mediated by the ERK/GSK3β/Snail pathway.

Growth and scintillation properties of Nd-doped Lu3Al5O12 single crystals by Czochralski and micro-pulling-down methods

The Nd-doped Lu3Al5O12 (Nd:LuAG) single crystal was grown by the Czochralski (CZ) method. In XRC profiles, the full-width at half-maximum (FWHM) value was 58arcsec, which was much higher than that of the μ-PD (194arcsec). In photo and radio-luminescence spectra, the CZ grown sample showed strong emission peaks attributed to Nd3+ 4f–4f transitions in visible wavelengths longer than 400nm. The Nd:LuAG grown with the CZ method showed light yield of 7900 photons/MeV, which is comparable with the standard BGO and energy resolution of 14% under 137Cs γ-ray excitation.

Scintillation properties of Tm-doped Lu 3Al 5O 12 single crystals

Using the micro-pulling-down (μ-PD) method, Tm-doped Lu 3Al 5O 12 (Tm:LuAG) single crystals were grown to examine their scintillation properties. In transmittance spectra, they exhibited about 80% transparency in the wavelengths longer than 320 nm and five absorption lines due to Tm 3+ 4f–4f transitions were observed. 241Am α-ray excited radioluminescence spectra were measured and intense 4f–4f emission peaks were observed with the host emission. When excited by 137Cs γ-Ray to obtain pulse height spectra, Tm 1% doped LuAG showed the highest light yield coupled with a photomultiplier (PMT) or a silicon avalanche photodiode (Si-APD). The light yield was estimated to be 5800 and 7300 photons/MeV for PMT and Si-APD, respectively. Decay time profiles consist of two exponential components and the fast and slow components are considered to be attributed to the host and the combination of the host and Tm 3+ 4f–4f emission, respectively.

Abstract 2509: Preclinical evaluation of the effects of cilengitide, an inhibitor of integrins, in sensitizing human solid cancer xenografts to radiation

Abstract Purpose: Integrins are implicated in resistance of solid tumors to therapies, including radiation therapy, suggesting that their inhibition would enhance efficacy of tumor therapy. Because cilengitide, a cyclic Arg-Gly-Asp (RGD)-derived peptide, inhibits αVβ3 and αVβ5 integrins, we investigated the efficacy of cilengitide in enhancing in vitro cancer cell radiosensitivity and in vivo radioresponse of cancer xenografts. Methods: Three non-small cell lung carcinoma lines (NSCLCs) (H460, A549 and H1299) and five head and neck squamous cell carcinoma lines (HNSCCs) (FaDu, SCC-15, SCC-25, HN-5 and UMSCC-1) cell lines were used for in vitro experiments. Of these, H460 and FaDu were used for in vivo testing when grown as xenografts in nude mice. The effects of cilengitide (1 – 50 µg/ml, 24 h) on in vitro cell viability was determined by MTS assay and on cellular radiosensitivity by clonogenic cell survival assay after exposing the cells to graded single doses of γ-radiation with or without cilengitide (given 1 h before and continued for 23 h after irradiation). In vivo effect of cilengitide on radioresponse of xenografts was assessed by tumor growth delay. When tumor xenografts reached 7 mm in diameter cilengitide treatment (30 or 60 mg/d/5days) was initiated followed by a single dose of 15 Gy local radiation (using 137Cs γ-ray source), when the tumors reached 8 mm. Results: Cilengitide (5µg/ml, 24 h) reduced in vitro viability of 7 out of 8 cell lines tested, which ranged between 71.4 ± 2.2% (SCC-15) and 27.8 ± 4.2% (H1299). In general, NSCLCs were more sensitive to cilengitide than HNSCCs. When combined with radiation, cilengitide significantly enhanced the radiosensitivity of all 3 NSCLC, by enhancement factors of 1.35 for H460, 1.56 for A549 and 1.3 for H1299. In contrast, cilengitide exerted only an additive effect on radiosensitivity of HNSCC lines. In vivo experiments showed that cilengitide as a single agent had no antitumor activity, but in combination with radiation it significantly enhanced response of both H460 (NSCLC) and FaDu (HNSCC) tumor xenografts. The enhancement factors were 1.7 for H460 and 2.0 for FaDu. Conclusion: The results showed that cilengitide reduced in vitro cell viability of lung and head and neck cancer cells but had no effect on tumor growth in vivo. When combined with radiation, the drug enhanced radiosensitivity of lung but not head and neck carcinoma cells. In contrast, cilengitide was highly effective in enhancing radiation response of both lung (H460) and head and neck (FaDu) tumor xenografts. These results suggest that cilengitide has potential to improve the treatment outcome of patients with NSCLC and HNSCC when combined with radiotherapy. Mechanistic studies addressing cilengitide-radiation interactions both in vitro and in vivo are underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2509. doi:10.1158/1538-7445.AM2011-2509

Effect of CCL1 antisense ODN on bacterial translocation in mice irradiated with whole body 137Cs γ-rays: elimination of M2b macrophages in translocation sites (111.19)

Abstract Mice irradiated with 5 Gy whole body 137Cs γ-rays (WBI-mice) are shown to be carriers of M2bMϕ (IL-10+CCL1+LIGHT+IL-12- Mϕ), which are inhibitory on the host antibacterial innate immunities in bacterial translocation. M2bMϕ maintain their suppressor cell properties through the production of CCL1. In this study, therefore, we tried to eliminate M2bMϕ from mesenteric lymph nodes (MLN) of WBI-mice by CCL1 antisense ODN gene therapy. WBI-mice were treated with CCL1 antisense ODN with various doses (2, 10, 50, or 250 μg/mouse), routes (i.p., i.m. or s.c.) and schedules (twice a day for 2 to 7 days, starting 1 to 4 weeks after γ-irradiation). F4/80+ MLN-Mϕ isolated from these mice were identified as M2bMϕ by their abilities to express intracellular IL-10 and LIGHT mRNA. As a control, MLN-Mϕ were isolated from WBI-mice treated with scrambled ODN and subjected to the same test. In the results, the numbers of MLN-M2bMϕ were greatly reduced in WBI-mice treated s.c. with 10 to 50 μg/mouse of CCL1 antisense ODN twice a day for 2 days, 5 days or 7 days, started 1 to 3 weeks after γ-irradiation. However, MLN-M2bMϕ were detected in WBI-mice treated with CCL1 antisense ODN twice a day for 2 days started 4 weeks after the irradiation. These results indicate that M2bMϕ are eliminated from MLN of WBI-mice s.c. treated with CCL1 antisense ODN twice a day for 2 days starting 1 to 3 weeks after γ-irradiation.

Effect of CCL1 antisense ODN on bacterial translocation in mice irradiated with whole body 137Cs γ-rays: induction of M1 macrophages in translocation sites (111.21)

Abstract M1Mϕ (IL-10-IL-12+ Mϕ) in mesenteric lymph nodes (MLN) of mice have been identified as major effector cells in the host defense against enterococcal translocation and subsequent sepsis. However, M1Mϕ are not easily generated in 5 Gy whole body γ-irradiated mice (WBI-mice) whose M2bMϕ (IL-10+CCL1+LIGHT+IL-12- Mϕ) predominate. M2bMϕ are inhibitory on resident Mϕ conversion to M1Mϕ. In our previous studies, M2bMϕ were not demonstrated in MLN of WBI-mice treated with CCL1 antisense ODN. In this study, therefore, we tried to induce M1Mϕ by enterococcal antigen in MLN of WBI-mice treated with CCL1 antisense ODN. WBI-mice were treated s.c. with CCL1 antisense ODN (10 μg/mouse) twice a day for 2 days starting 2 weeks after γ-irradiation. One day after the final treatment, these mice were stimulated orally with 107 heat-killed E. faecalis. Two days after stimulation, F4/80+ MLN-Mϕ were isolated from these mice and tested for their M1Mϕ properties based on their abilities to express intracellular IL-12, CXCL9 and iNOS mRNA. In the results, Mϕ from WBI-mice treated with scrambled ODN did not express iNOS mRNA, intracellular IL-12 and CXCL9, even when these mice were stimulated with enterococcal antigen. However, iNOS+IL-12+CXCL9+ Mϕ were isolated from the same antigen-stimulated WBI-mice treated with CCL1 antisense ODN. These results indicate that M1Mϕ are inducible by the enterococcal antigen in WBI-mice treated with CCL1 antisense ODN.

Ionising radiation triggers fat accumulation in white adipose tissue

Purpose: To investigate changes in gonadal white adipose tissue and lipogenesis-related gene expression induced by radiation exposure.Materials and methods: Groups of two-month-old C57BL/6 mice were exposed whole-body to 137Cs γ-rays at a single dose (5 gray [Gy]) or fractionated doses (1 Gy × 5 times, 0.5 Gy × 10 times, or 0.2 Gy × 25 times). Six months after irradiation, gonadal white adipose tissue was isolated from mice. Two and 25-month-old mice were used as young and old study references. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure messenger RNA (mRNA) expression of genes related to: (i) Primary lipid metabolism (ATP-citrate lyase [ACL], malic enzyme1 [ME1] and glucose-6-phosphate dehydrogenase 2 [G6PD2]), (ii) glucose uptake (glucose transporter 4 [GLUT4]), (iii) fatty acid synthesis (sterol regulatory element binding transcription factor 1 [SREBP-1c], fatty acid synthetase [FAS] and acetyl-coenzyme A carboxylase beta [ACC]), (iv) triglyceride synthesis (diacylglycerol O-acyltransferase 1 [DGAT1] and diacylglycerol O-acyltransferase 2 [DGAT2]), and (v) adipose-derived hormones (leptin [LEP]).Results: The weight of gonadal white adipose tissue in the irradiated groups tended to increase compared to the non-irradiated group though the radiation-induced increase in white adipose tissue was only significant for the 5 × 1 Gy group. The mRNA levels of SREBP-1c, ACC, FAS, ACL, GLUT4, ME1 and G6PD2 were relatively lower in γ-irradiated groups than in non-irradiated groups. The mRNA levels of leptin and DGAT were relatively higher than non-irradiated groups. The changes in expression of these lipogenesis-related genes caused by γ-irradiation showed a very similar pattern to changes caused by ageing.Conclusions: A physical agent such as γ-rays can trigger biological responses resulting in fat accumulation of gonadal white adipose tissue in mice.

Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage

Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints.Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (137Cs γ-rays) of cells exposed to various concentrations of methylproamine. Uptake of methylproamine into cell nuclei was measured in parallel.Results: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM.Conclusions: These results are consistent with the hypothesis that radioprotection by methylproamine is mediated by attenuation of the extent of initial DNA damage.

Structural chromosomal aberrations, aneuploidy, and mosaicism in early cleavage mouse embryos derived from spermatozoa exposed to γ-rays

Purpose: To quantitatively and qualitatively investigate the changes in chromosomal aberrations during early cleavage in mouse embryos derived from γ-irradiated spermatozoa.Materials and methods: Mature males were exposed to 2 Gy or 4 Gy of 137Cs γ-rays, and their spermatozoa were used to produce embryos via in vitro fertilisation (IVF). The metaphase chromosomes were prepared from one-cell, two-cell, and four-cell embryos. In the chromosome preparations from two-cell and four-cell embryos, the separation of the sister blastomeres was precluded by treatment of the embryos with concanavalin A. The incidence of embryos with structural chromosomal aberrations, aneuploidy, or mosaicism was estimated. The fates of the different types of γ-ray-induced structural chromosomal aberrations were also investigated in those embryos.Results: The exposure of spermatozoa to 2 Gy or 4 Gy γ-rays caused structural chromosomal aberrations in 25.9% and 35.7% of the resultant one-cell embryos, respectively. At two-cell embryonic stage, the incidence of structural chromosomal aberrations was 17.4% in the 2 Gy group and 27.1% in the 4 Gy group. At the four-cell embryonic stage, although the incidence of control embryos with structural chromosomal aberrations was considerably high, the net incidence of embryos with radiation-induced structural chromosomal aberrations was similar to that at the one-cell stage. The incidence of aneuploidy was high in two-cell and four-cell embryos after both doses of γ-rays. The incidence of mosaicism increased significantly in dose- and embryonic-stage-dependent manners. Anaphase lag, and the degeneration and non-disjunction of the aberrant chromosomes were frequently observed in aneuploid and mosaic embryos.Conclusions: Mouse sperm DNA is highly vulnerable to γ-rays. The structural chromosomal aberrations of sperm origin are unstable in their behaviour and structure during cleavage, and therefore cause secondary aneuploidy and mosaicism in the early cleavage embryos.

The effect of human cord blood therapy on the intestinal tract of lethally irradiated mice: Possible use for mass casualties

Purpose: To evaluate the recovery of the gastrointestinal tract in lethally irradiated mice treated with human cord blood and antibiotics.Materials and methods: A/J mice were randomly assigned to seven study groups, including groups exposed to acute 9 Gy from 137Cs γ-rays to the whole body. Four hours after irradiation, exposed mice were treated with either cord blood nucleated cells, Levaquin, or a combination of both. Weight gain/loss and survival were monitored for 2 months. Upon death or euthanasia, the organs were prepared for molecular and histological analyses.Results: Whereas irradiated mice (n = 9) lived 6–15 days, ∼ 60% of irradiated mice that received the combined treatment (n = 7) survived more than 50 days. None of the treated animals developed Graft versus Host disease. All animals lost weight after irradiation; however, the 50+ days-survivors (n = 4) gained on average ∼1.8 g over their initial weight. Whereas hemorrhagic bone marrow and large areas of transmural necrosis were observed in the bowel of the irradiated mice, the 50+ days-survivors showed recovery of the bone marrow. They behaved normally and had significant but incomplete recovery of the intestinal and colonic mucosa. Human DNA was detected in their organs, particularly in the large intestine.Conclusion: Red cell-depleted cord blood transfusions combined with antibiotic treatment contribute to bone marrow and gastrointestinal recovery in high dose-irradiated mice, and may be an available therapy for mass casualties during radiological emergencies.

Effects of fission neutrons on human thyroid tissues maintained in SCID mice

Morphology and function (secretion of thyroid hormone) of human thyroid tissues from Graves’ disease patients are well maintained in C57BL/6J- scid mice. Serum level of thyroid hormone was reduced by fission neutrons from the nuclear reactor UTR-KINKI, and changes in thyroid hormone by fission neutrons were bigger than those by low LET radiations, X-rays and 137Cs γ-rays, suggesting high relative biological effectiveness (RBE; 6.5) of fission neutrons. Microarray analyses revealed that about 3% of genes showed more than 4-fold change in gene expression in the unexposed thyroid tissues against surgically resected thyroid tissues from the same patient, probably due to the difficult oxygen and nutrient supply shortly after transplantation. Dose-dependent changes in gene expression against unexposed concurrent controls were observed with increasing doses of fission neutrons (0.2–0.6 Gy) and 137Cs γ-rays (1.0–3.0 Gy) and showed high RBE (4.2). Furthermore, there were some specific genes which showed more than 4-fold change in gene expression in all the thyroid tissues exposed to higher doses of radiation, especially neutrons (0.4 and 0.6 Gy), but none at lower doses (0.2 Gy of neutrons and 1.0 and 2.0 Gy of γ-rays). These genes related to degeneration, regeneration, apoptosis, and transcription, respond specifically and very sensitively to neutron injury in human thyroid tissues. This is the first experimental report that fission neutrons can induce some morphological and functional disorders in human tissues, showing high RBE against γ-ray exposure. These results are useful to evaluate the risks of fission neutrons and cosmic rays to humans.

Inter-individual variation in DNA double-strand break repair in human fibroblasts before and after exposure to low doses of ionizing radiation

DNA double-strand breaks (DSB) are generally considered the most critical lesion induced by ionizing radiation (IR) and may initiate carcinogenesis and other disease. Using an immunofluorescence assay to simultaneously detect nuclear foci of the phosphorylated forms of histone H2AX and ATM kinase at sites of DSBs, we examined the response of 25 apparently normal and 10 DNA repair-deficient ( ATM, ATR, NBN, LIG1, LIG4, and FANCG) primary fibroblast strains irradiated with low doses of 137Cs γ-rays. Quiescent G 0/G 1-phase cultures were exposed to 5, 10, and 25 cGy and allowed to repair for 24 h. The maximum level of IR-induced foci (0.15 foci per cGy, at 10 or 30 min) in the normal strains showed much less inter-individual variation (CV ≈ 0.2) than the level of spontaneous foci, which ranged from 0.2–2.6 foci/cell (CV ≈ 0.6; mean ± SD of 1.00 ± 0.57). Significantly slower focus formation post-irradiation was observed in seven normal strains, similar to most mutant strains examined. There was variation in repair efficiency measured by the fraction of IR-induced foci remaining 24 h post-irradiation, curiously with the strains having slower focus formation showing more efficient repair after 25 cGy. Interestingly, the ranges of spontaneous and residual induced foci levels at 24 h in the normal strains were as least as large as those observed for the repair-defective mutant strains. The inter-individual variation in DSB foci parameters observed in cells exposed to low doses of ionizing radiation in this small survey of apparently normal people suggests that hypomorphic genetic variants in genomic maintenance and/or DNA damage signaling and repair genes may contribute to differential susceptibility to cancer induced by environmental mutagens.

Comparison of the standards for air kerma of the ITN (Portugal) and the BIPM for 137Cs γ-rays

A first comparison of the standards for air kerma of the Instituto Tecnológico e Nuclear (ITN), Portugal and of the Bureau International des Poids et Mesures (BIPM) has been carried out in 137Cs gamma radiation. The comparison result, expressed as a ratio of the ITN standard and the recently re-evaluated BIPM standard, is 1.0013 (0.0021).Main text.To reach the main text of this paper, click on Final Report.Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/.The final report has been peer-reviewed and approved for publication by the CCRI Section I, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

PPARα ligands inhibit radiation-induced microglial inflammatory responses by negatively regulating NF-κB and AP-1 pathways

Whole-brain irradiation (WBI) can lead to cognitive impairment several months to years after irradiation. Studies on rodents have shown a rapid and sustained increase in activated microglia (brain macrophages) following brain irradiation, contributing to a chronic inflammatory response and a corresponding decrease in hippocampal neurogenesis. Thus, alleviating microglial activation following radiation represents a key strategy to minimize WBI-induced morbidity. We hypothesized that pretreatment with peroxisomal proliferator-activated receptor (PPAR)α agonists would ameliorate the proinflammatory responses seen in the microglia following in vitro radiation. Irradiating BV-2 cells (a murine microglial cell line) with single doses (2–10 Gy) of 137Cs γ-rays led to increases in (1) the gene expression of IL-1β and TNFα, (2) Cox-2 protein levels, and (3) intracellular ROS generation. In addition, an increase in the DNA-binding activity of redox-regulated proinflammatory transcription factors AP-1 and NF-κB was observed. Pretreating BV-2 cells with the PPARα agonists GW7647 and Fenofibrate significantly inhibited the radiation-induced microglial proinflammatory response, in part, via decreasing (i) the nuclear translocation of the NF-κB p65 subunit and (ii) phosphorylation of the c-jun subunit of AP-1 in the nucleus. Taken together, these data support the hypothesis that activation of PPARα can modulate the radiation-induced microglial proinflammatory response.

Differential radiation sensitivity to morphological, functional and molecular changes of human thyroid tissues and bone marrow cells maintained in SCID mice

Morphology and function of human organs and tissues are well maintained in the improved SCID (severe combined immunodeficient) mice for a long period (∼3 years). To study the radiation-induced damage on human thyroid gland, human thyroid tissues transplanted to SCID mice were consecutively exposed to X-rays or 137Cs γ-rays at high and low dose rates for approximately 2 years. Consecutive irradiation resulted in the disappearance of follicles and significant decrease of thyroid hormone secretion. Mutations in p53 and c-kit genes were induced significantly in human thyroid tissues from old head and neck cancer patients (av. 56.8 years, 4 males) and a Graves’ disease patient (20 years, male) over the dose of 24 Gy (44.7 ± 5.9 Gy, mean ± S.E) and 11 Gy (20.2 ± 7.8 Gy), respectively, while mutations were not detected at lower doses nor in unexposed matched controls ( p < 0.01). There were significant differences in mutation frequency in the transplanted human thyroid tissues (31 years, female) between high dose rate (1.19 Gy/min; 8 in 20 tissues) and low dose rate (0.00023 Gy/min; 0 in 14 tissues) exposures ( p < 0.01). Mutations were not detected in RET, K- ras and β-catenin genes. Expression analysis by GeneChip indicated that gene expression was also well maintained in the transplanted human thyroid tissues. However, lower doses (1 or 3 Gy) of 137Cs γ-rays can induce changes in gene expression in the transplanted human thyroid tissues. Furthermore, fatally irradiated SCID mice could survive with human bone marrow cell transplantation. When about half of mouse bone marrows were replaced by human bone marrow cells, the human bone marrow cells showed high sensitivity to γ-irradiation; 28.0% and 0.45% survival after 0.5 and 2.0 Gy exposures, respectively.

Scintillation Properties of Ba0.20Sr0.80Cl2 Single Crystal

New scintillation crystal of a Ba0.20Sr0.80Cl2 grown by the Czochralski technique is reported. The grown crystal was cut into a size of 10×10×10 mm3. The lattice parameter of the grown crystal is a = b = c = 7.041 Å and the crystal structure is cubic. The luminescence and scintillation properties of the Ba0.20Sr0.80Cl2 crystal were studied. The luminescent characteristics were measured with ultraviolet (UV) light and X-ray source to study the emission spectra of the crystal. Scintillation properties of the crystal such as pulse height spectra, energy resolution, α/β ratio, light output, proportionality curve, and fluorescence decay time were measured with the various radioactive γ-ray sources and α-source at room temperature. The light output of the crystal was compared with that of the CsI(Tl) crystal and the absolute light output was measured with avalanche photodiode (APD). While the light output of the crystal was less than that of the CsI(Tl), the energy resolution was approximately 6.9% for 137Cs 662 keV γ-ray with PMT which is similar to that of the CsI(Tl) crystal for 137Cs γ-rays.

Properties of ZnSe:Te,O Crystals Grown by Bridgman-Stockbarger Method

Zinc selenide crystals were grown in graphite crucibles by the Bridgman–Stockbarger method in a vertical compression furnace under argon pressure of 5×106 Pa. From the absorption spectra, the band gap energies of the ZnSe single crystals were calculated by a linear fitting process. The maximum wavelength of the emission spectrum of the ZnSe:Te,O scintillator was 630 nm, which was well matched with the response wavelength of the Si photodiode. The energy resolution of the ZnSe:Te,O scintillator was 11.9% when it was exposed to 137Cs γ-ray. Its size was 10×10×1 mm3. The afterglow level of the ZnSe:Te,O scintillator after 5 ms was 0.023%. The relative light output of the ZnSe:Te,O scintillator was 2.167 times higher than CsI:Tl. The luminescence decay time of the ZnSe:Te,O scintillator has two exponential components with 27 and 84 γs time constant.

Growth and Characteristics of Gd2SiO5 Crystal Doped Ce3&

Gadolinium oxyorthsilicate doped with cerium, Gd2SiO5:Ce (GSO:Ce), is a scintillator crystal discovered in 1983, which has excellent properties, high light yield, fast decay time, and good radiation hardness. The Gd2SiO5 (GSO) and GSO:Ce (0.5 mole%) single crystals were grown by Czochralski method under argon atmosphere. After the growth, thermal treatment of the GSO crystals was carried out at 1780K for 3 hours under argon atmosphere. The maximum wavelength of the emission spectrum of the GSO:Ce scintillator was 430 nm. The energy resolution of the GSO:Ce scintillator was 9.1 % with PMT, when it was exposed to 137Cs γ-ray. The luminescence decay time of the GSO:Ce scintillator has two exponential components with 68.7 ns and 754 ns time constant.

Synthesis and application of molecular probe for detection of hydroxyl radicals produced by Na125I and gamma-rays in aqueous solution

Purpose: To synthesize N-(3-(3-aminopropylamino)propyl)-2-oxo-2H-chromene-3-carboxamide (7), a novel DNA-binding, coumarin-based, fluorescent hydroxylradical (•OH) indicator and to assess its quantum efficiency compared with that of coumarin-3-carboxylic acid (1) and N1,N12-bis[2-oxo-2H-chromene-3-carbonyl]- 1,12-diamine-4,9-diazadodecane (9).Materials and methods: Using computer-generated molecular modeling, 7 and 9 and their respective 7-hydroxylated derivatives 8 and 10 were docked onto DNA dodecamer d(CGCGAATTCGCG)2, the ligand–DNA complexes were energy minimized, and binding free energies and inhibition constants were calculated. Compound 7 was judged an appropriate target molecule and was synthesized. Compounds 1, 7, and 9 were incubated with Na125I or irradiated with 137Cs γ-rays, and the influence of pH, dose, type of radiation, and the concentration of indicator on fluorescence yield were determined.Results: Non-fluorescent 7 and 9 are converted to fluorescent, 7-hydroxylated derivatives 8 and 10 after interaction with •OH in aqueous solution. For 1, 7, and 9, hydroxylation yield increases linearly with both Na125I dose (0–700×106 decays) and 137Cs dose (0–11.0 Gy). Fluorescence induction is significantly reduced at acidic pH and the fluorescent quantum yield of 8 is ∼3 times that of 2 or 10 at pH 7.0. With Na125I incubation and γ-ray irradiation, the fluorescence signal of 7 increases linearly with concentration and saturates at ∼50 μM.Conclusion: Compound 7 quantifies lower concentrations of •OH than do 1 and 9. This detector is therefore likely to be a good reporter of •OH produced within a few nanometers of DNA.