Protective Effects and Mechanisms of Huangqi Decoction Against Radiation-Induced Bystander Effects / Efectos Protectores y Mecanismos de la Decocción de Huangqi Contra los Efectos Secundarios Inducidos por la Radiación

SUMMARY: The 12C6+ heavy ion beam irradiation can cause bystander effects. The inflammatory cytokines, endocrine hormones and apoptotic proteins may be involved in 12C6+ irradiation-induced bystander effects. This study characterized the protective effects and mechanisms of Huangqi decoction (HQD) against 12C6+ radiation induced bystander effects. Wistar rats were randomly divided into control, 12C6+ heavy ion irradiation model, and high-dose/medium-dose/low-dose HQD groups. HE staining assessed the pathological changes of brain and kidney. Peripheral blood chemical indicators as well as inflammatory factors and endocrine hormones were detected. Apoptosis was measured with TUNEL. Proliferating cell nuclear antigen (PCNA) expression was determined with real-time PCR and Western blot.Irradiation induced pathological damage to the brain and kidney tissues. After irradiation, the numbers of white blood cells (WBC) and monocyte, and the expression of interleukin (IL)-2, corticotropin-releasing hormone (CRH) and PCNA decreased. The damage was accompanied by increased expression of IL-1β, IL-6, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) as well as increased neuronal apoptosis. These effects were indicative of radiation-induced bystander effects. Administration of HQD attenuated the pathological damage to brain and kidney tissues, and increased the numbers of WBC, neutrophils, lymphocyte and monocytes, as well as the expression of IL-2, CRH and PCNA. It also decreased the expression of IL-1β, IL-6, CORT and ACTH as well as neuronal apoptosis. HQD exhibits protective effects against 12C6+ radiation-induced bystander effects. The underlying mechanism may involve the promotion of the production of peripheral blood cells, inhibition of inflammatory factors and apoptosis, and regulation of endocrine hormones.

La irradiación con haz de iones pesados 12C6+ puede provocar efectos secundarios. Las citoquinas inflamatorias, las hormonas endocrinas y las proteínas apoptóticas pueden estar involucradas en los efectos secundarios inducidos por la irradiación 12C6+. Este estudio caracterizó los efectos y mecanismos protectores de la decocción de Huangqi (HQD) contra los efectos externos inducidos por la radiación 12C6+. Las ratas Wistar se dividieron aleatoriamente en grupos control, modelo de irradiación de iones pesados 12C6+ y grupos de dosis alta/media/baja de HQD. La tinción con HE evaluó los cambios patológicos del cerebro y el riñón. Se detectaron indicadores químicos de sangre periférica, así como factores inflamatorios y hormonas endocrinas. La apoptosis se midió con TUNEL. La expresión del antígeno nuclear de células en proliferación (PCNA) se determinó mediante PCR en tiempo real y transferencia Western blot. La irradiación indujo daños patológicos en los tejidos cerebrales y renales. Después de la irradiación, disminuyó el número de glóbulos blancos (WBC) y monocitos, y la expresión de interleucina (IL)-2, hormona liberadora de corticotropina (CRH) y PCNA. El daño estuvo acompañado por una mayor expresión de IL-1β, IL-6, corticosterona (CORT) y hormona adrenocorticotrópica (ACTH), así como un aumento de la apoptosis neuronal. Estas alteraciones fueron indicativas de efectos inducidos por la radiación. La administración de HQD atenuó el daño patológico a los tejidos cerebrales y renales, y aumentó el número de leucocitos y monocitos, así como la expresión de IL-2, CRH y PCNA. También disminuyó la expresión de IL-1β, IL-6, CORT y ACTH, así como la apoptosis neuronal. HQD exhibe mecanismos protectores contra los efectos externos inducidos por la radiación 12C6+. El mecanismo subyacente puede implicar la promoción de la producción de células sanguíneas periféricas, la inhibición de factores inflamatorios y la apoptosis y la regulación de hormonas endocrinas.

Evidence of Hexadecapole Deformation in Uranium-238 at the Relativistic Heavy Ion Collider.

State-of-the-art hydrodynamic simulations of the quark-gluon plasma are unable to reproduce the elliptic flow of particles observed at the BNL Relativistic Heavy Ion Collider (RHIC) in relativistic ^{238}U+^{238}U collisions when they rely on information obtained from low-energy experiments for the implementation of deformation in the colliding ^{238}U ions. We show that this is due to an inappropriate treatment of well-deformed nuclei in the modeling of the initial conditions of the quark-gluon plasma. Past studies have identified the deformation of the nuclear surface with that of the nuclear volume, though these are different concepts. In particular, a volume quadrupole moment can be generated by both a surface hexadecapole and a surface quadrupole moment. This feature was so far neglected in the modeling of heavy-ion collisions, and is particularly relevant for nuclei like ^{238}U, which is both quadrupole deformed and hexadecapole deformed. With rigorous input from Skyrme density functional calculations, we show that correcting for such effects in the implementation of nuclear deformations in hydrodynamic simulations restores agreement with BNL RHIC data. This brings consistency to the results of nuclear experiments across energy scales, and demonstrates the impact of the hexadecapole deformation of ^{238}U on high-energy collisions.

[Breeding of new Artemisia annua variety "Kehao No.1"].

As a natural plant source of artemisinin,a first-line drug against malaria,Artemisia annua directly affects the extraction process of artemisinin and the source of artemisinin. At present,traditional breeding methods combined with tissue culture are often used to breed high-yield artemisinin-containing new varieties of A. annua. However,the breeding method has the disadvantages of low efficiency and continuous selection. In this study,heavy ion beam irradiation technology was used to observe the specific germplasm resources of A. annua,and the morphological characteristics,agronomic traits and artemisinin content were used as indicators to observe the selection materials and materials. The cultivated new varieties were compared with trials and regional trials. In addition,the new variety of A. annua was identified by SRAP molecular marker technology. The results showed that the new variety of A. annua, " Kehao No.1",had an average yield of 235. 0 kg of dry leaf per mu,which was more than 20% higher than that of the control. Especially,the average artemisinin content was 2. 0%,which was 45% higher than that of the control,and the " Kehao No.1" has high anti-white powder disease,high-yield and high-quality new varieties. Therefore,mutagenic breeding of heavy ion beam irradiation can significantly improve the yield and artemisinin content of the " Kehao No. 1" and it has a good promotion value.

MECHANISTIC MODELING PREDICTS NO SIGNIFICANT DOSE RATE EFFECT ON HEAVY-ION CARCINOGENESIS AT DOSE RATES RELEVANT FOR SPACE EXPLORATION.

Heavy ion-induced carcinogenesis is a challenge for human space exploration, and mechanistically-motivated mathematical models are needed to predict space-relevant low dose-rate risks, which are difficult to measure experimentally, based on data at higher dose rates. We present such a model, which quantifies targeted and non-targeted radiation effects. We fitted it to lung carcinogenesis data in radon-exposed miners and rats, which provide valuable information on carcinogenesis from protracted exposure to densely-ionizing radiation. We generated model-based estimates for the dose-rate-effect, relative to acute exposures, on heavy ion-induced carcinogenesis at doses/dose rates expected during a Mars mission. A small and not statistically-significant dose-rate effect was predicted: 1.00 (95% CI: 0.54, 1.40) for human data and for combined human and rat data 0.93 (0.06, 1.49). Consequently, heavy ion carcinogenesis estimates from moderate/high dose-rate experimental data may be applicable to doses/dose rates relevant for space exploration.

Curcumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways.

Oxidative stress is one of the major mechanisms implicated in carbon ion irradiation. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its effects partly radioprotection. In vivo, we investigated the protective effects of curcumin against (12)C(6+)radiation-induced cerebral injury. Our results showed that 4Gy heavy ion radiation-induced spatial strategy and memory decline and reduction of brain superoxide dismutase (SOD) activity levels were all consistently improved by curcumin, and the augmentation of cerebral malonaldehyde (MDA) was lowered by curcumin. Furthermore, both the cerebral cells nuclear erythroid 2-related factor 2 (Nrf2) protein and three typically recognized Nrf2 downstream genes, NAD(P)H quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), and γ-glutamyl cysteine synthetase (γ-GCS) were consistently up-regulated in curcumin-pretreated mice. Our study confirmed the antagonistic roles of curcumin to counteract radiation-induced cerebral injury in vivo and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against radiation. This provides a potential useful radioprotection dietary component for human populations.

Isolation, morphological and molecular characterization of phytate-hydrolysing fungi by 18S rDNA sequence analysis

Phytate is the primary storage form of phosphate in plants. Monogastric animals like poultry, pigs and fishes have very low or no phytase activities in their digestive tracts therefore, are incapable to efficiently utilize phytate phosphorus from the feed. Phytase from microbial sources are supplemented to feedstuff of these to increase the uptake of phytate phosphorus. In the present work efforts were made to isolate and characterize proficient phytase producing fungi from soil. Phytase producing fungi were isolated using phytate specific medium. Fungal isolates were selected according to their higher phytase activities. These isolates were further characterized and identified by morphological and microscopic analysis and confirmed by amplification of 18S rRNA gene, using specific primers. This gene was subsequently sequenced and phylogenetic affiliations were assigned. Fungal isolates were identified as various species of Aspergillus. Phytases from these fungi could be utilized as a feed additive in poultry and swine industries.

Adaptive response of low linear energy transfer X-rays for protection against high linear energy transfer accelerated heavy ion-induced teratogenesis.

BACKGROUND: Adaptive response (AR) of low linear energy transfer (LET) irradiations for protection against teratogenesis induced by high LET irradiations is not well documented. In this study, induction of AR by X-rays against teratogenesis induced by accelerated heavy ions was examined in fetal mice. METHODS: Irradiations of pregnant C57BL/6J mice were performed by delivering a priming low dose from X-rays at 0.05 or 0.30 Gy on gestation day 11 followed one day later by a challenge high dose from either X-rays or accelerated heavy ions. Monoenergetic beams of carbon, neon, silicon, and iron with the LET values of about 15, 30, 55, and 200 keV/µm, respectively, were examined. Significant suppression of teratogenic effects (fetal death, malformation of live fetuses, or low body weight) was used as the endpoint for judgment of a successful AR induction. RESULTS: Existence of AR induced by low-LET X-rays against teratogenic effect induced by high-LET accelerated heavy ions was demonstrated. The priming low dose of X-rays significantly reduced the occurrence of prenatal fetal death, malformation, and/or low body weight induced by the challenge high dose from either X-rays or accelerated heavy ions of carbon, neon or silicon but not iron particles. CONCLUSIONS: Successful AR induction appears to be a radiation quality event, depending on the LET value and/or the particle species of the challenge irradiations. These findings would provide a new insight into the study on radiation-induced AR in utero.

Amorphization of nanocrystalline monoclinic ZrO2 by swift heavy ion irradiation.

Bulk ZrO(2) polymorphs generally have an extremely high amorphization tolerance upon low energy ion and swift heavy ion irradiation in which ballistic interaction and ionization radiation dominate the ion-solid interaction, respectively. However, under very high-energy irradiation by 1.33 GeV U-238, nanocrystalline (40-50 nm) monoclinic ZrO(2) can be amorphized. A computational simulation based on a thermal spike model reveals that the strong ionizing radiation from swift heavy ions with a very high electronic energy loss of 52.2 keV nm(-1) can induce transient zones with temperatures well above the ZrO(2) melting point. The extreme electronic energy loss, coupled with the high energy state of the nanostructured materials and a high thermal confinement due to the less effective heat transport within the transient hot zone, may eventually be responsible for the ionizing radiation-induced amorphization without transforming to the tetragonal polymorph. The amorphization of nanocrystalline zirconia was also confirmed by 1.69 GeV Au ion irradiation with the electronic energy loss of 40 keV nm(-1). These results suggest that highly radiation tolerant materials in bulk forms, such as ZrO(2), may be radiation sensitive with the reduced length scale down to the nano-metered regime upon irradiation above a threshold value of electronic energy loss.

Volume-of-interest cone-beam CT using a 2.35 MV beam generated with a carbon target.

PURPOSE: This is a proof-of-concept study addressing volume of interest (VOI) cone beam CT (CBCT) imaging using an x-ray beam produced by 2.35 MeV electrons incident on a carbon linear accelerator target. Methodology is presented relevant to VOI CBCT image acquisition and reconstruction. Sample image data are given to demonstrate and compare two approaches to minimizing artifacts arising from reconstruction with truncated projections. Dosimetric measurements quantify the potential dose reduction of VOI acquisition relative to full-field CBCT. The dependence of contrast-to-noise ratio (CNR) on VOI dimension is investigated. METHODS: A paradigm is presented linking the treatment planning process with the imaging technique, allowing definition of an imaging VOI to be tailored to the geometry of the patient. Missing data in truncated projection images are completed using a priori information in the form of digitally reconstructed radiographs (DRRs) generated from the planning CT set. This method is compared to a simpler technique of extrapolating truncated projection data prior to reconstruction. The utility of these approaches is shown through imaging of a geometric phantom and the head-and-neck section of a lamb. The total scatter factor of the 2.35 MV∕carbon beam on field size is measured and compared to a standard therapeutic beam to estimate the comparative dose reduction inside the VOI. Thermoluminescent dosimeters and Gafchromic film measurements are used to compare the imaging dose distributions for the 2.35 MV∕carbon beam between VOI and full-field techniques. The dependence of CNR on VOI dimension is measured for VOIs ranging from 4 to 15 cm diameter. RESULTS: Without compensating for missing data outside of truncated projections prior to reconstruction, pronounced boundary artifacts are present, in three dimensions, within 2-3 cm of the edges of the VOI. These artifacts, as well as cupping inside the VOI, can be reduced substantially using either the DRR filling or extrapolation techniques presented. Compared to 6 MV, the 2.35 MV∕carbon beam shows a substantially greater dependence of total scatter factor on field size, indicating a comparative advantage of the VOI approach when combined with the low-Z target beam. Dosimetric measurements in the anthropomorphic head phantom demonstrate a dose reduction by up to 15% and 75% inside and outside of the VOI, respectively, compared to full-field imaging. For the 2.35 MV∕carbon beam, CNR was shown to be approximately invariant with VOI dimension for bone and lung objects. CONCLUSIONS: The low-Z target, VOI CBCT technique appears to be feasible and combines the desirable characteristics of the low-Z target beam with regard to CNR, with the capacity to localize the imaging dose to the anatomy relevant to the image guidance task.

Analytical modeling of relative luminescence efficiency of Al2O3:C optically stimulated luminescence detectors exposed to high-energy heavy charged particles.

The objective of this work is to test analytical models to calculate the luminescence efficiency of Al(2)O(3):C optically stimulated luminescence detectors (OSLDs) exposed to heavy charged particles with energies relevant to space dosimetry and particle therapy. We used the track structure model to obtain an analytical expression for the relative luminescence efficiency based on the average radial dose distribution produced by the heavy charged particle. We compared the relative luminescence efficiency calculated using seven different radial dose distribution models, including a modified model introduced in this work, with experimental data. The results obtained using the modified radial dose distribution function agreed within 20% with experimental data from Al(2)O(3):C OSLDs relative luminescence efficiency for particles with atomic number ranging from 1 to 54 and linear energy transfer in water from 0.2 up to 1368 keV µm(-1). In spite of the significant improvement over other radial dose distribution models, understanding of the underlying physical processes associated with these radial dose distribution models remain elusive and may represent a limitation of the track structure model.

Bound exciton photoluminescence from ion­implanted phosphorus in thin silicon layers.

We report the observation of clear bound exciton (BE) emission from ion-implanted phosphorus. Shallow implantation and high-temperature annealing successfully introduce active donors into thin silicon layers. The BE emission at a wavelength of 1079 nm shows that a part of the implanted donors are definitely activated and isolated from each other. However, photoluminescence and electron spin resonance studies find a cluster state of the activated donors. The BE emission is suppressed by this cluster state rather than the nonradiative processes caused by ion implantation. Our results provide important information about ion implantation for doping quantum devices with phosphorus quantum bits.

Heavy ion irradiation and unloading effects on mouse lumbar vertebral microarchitecture, mechanical properties and tissue stresses.

Astronauts are exposed to both musculoskeletal disuse and heavy ion radiation in space. Disuse alters the magnitude and direction of forces placed upon the skeleton causing bone remodeling, while energy deposited by ionizing radiation causes free radical formation and can lead to DNA strand breaks and oxidative damage to tissues. Radiation and disuse each result in a net loss of mineralized tissue in the adult, although the combined effects, subsequent consequences for mechanical properties and potential for recovery may differ. First, we examined how a high dose (2 Gy) of heavy ion radiation ((56)Fe) causes loss of mineralized tissue in the lumbar vertebrae of skeletally mature (4 months old), male, C57BL/6 mice using microcomputed tomography and determined the influence of structural changes on mechanical properties using whole bone compression tests and finite element analyses. Next, we tested if a low dose (0.5 Gy) of heavy particle radiation prevents skeletal recovery from a 14-day period of hindlimb unloading. Irradiation with a high dose of (56)Fe (2 Gy) caused bone loss (-14%) in the cancellous-rich centrum of the fourth lumbar vertebra (L4) 1 month later, increased trabecular stresses (+27%), increased the propensity for trabecular buckling and shifted stresses to the cortex. As expected, hindlimb unloading (14 days) alone adversely affected microarchitectural and mechanical stiffness of lumbar vertebrae, although the reduction in yield force was not statistically significant (-17%). Irradiation with a low dose of (56)Fe (0.5 Gy) did not affect vertebrae in normally loaded mice, but significantly reduced compressive yield force in vertebrae of unloaded mice relative to sham-irradiated controls (-24%). Irradiation did not impair the recovery of trabecular bone volume fraction that occurs after hindlimb unloaded mice are released to ambulate normally, although microarchitectural differences persisted 28 days later (96% increase in ratio of rod- to plate-like trabeculae). In summary, (56)Fe irradiation (0.5 Gy) of unloaded mice contributed to a reduction in compressive strength and partially prevented recovery of cancellous microarchitecture from adaptive responses of lumbar vertebrae to skeletal unloading. Thus, irradiation with heavy ions may accelerate or worsen the loss of skeletal integrity triggered by musculoskeletal disuse.

Induction of micronuclei in germinating onion seed root tip cells irradiated with high energy heavy ions.

Effects of high LET charged particles on a perfect in-vivo system are an essential theme for the study of the biological effects of radiation. Germinating onion seeds are independent complete organisms and the radiation induced micronuclei in the root chip cells can be examined quantitatively and theoretically. We irradiated with three types of high energy accelerated heavy ions germinating onion seeds using a synchrotron and observed micronuclei in the root tip cells. Micronuclei induction showed characteristic dose responses of an upward convex bell shape and a steep rise near zero doses for all types of the ions. The bell curve dose responses, however, could be explained by a simple mathematical model. A parameter in the model which indicates micronuclei induction frequency and another parameter which indicates induction frequency of lethal damages (or damages delaying cell divisions) per heavy ion track were both proportional to square of the LET. Because we suspected by-stander effect concerning the dose responses rising steeply near zero doses and tapering off for higher doses, we tested acute irradiation to remove time of information transmittance between cells using a single spill (about 0.3 s) of the synchrotron beam. No difference was detected between normal multiple spill irradiations and single spill.

Biophysical modeling of fragment length distributions of DNA plasmids after X and heavy-ion irradiation analyzed by atomic force microscopy.

The investigation of fragment length distributions of plasmid DNA gives insight into the influence of localized energy distribution on the induction of DNA damage, particularly the clustering of double-strand breaks. We present an approach that determines the fragment length distributions of plasmid DNA after heavy-ion irradiation by using the Local Effect Model. We find a good agreement of our simulations with experimental fragment distributions derived from atomic force microscopy (AFM) studies by including experimental constraints typical for AFM. Our calculations reveal that by comparing the fragmentation in terms of fluence, we can uniquely distinguish the effect of different radiation qualities. For very high-LET irradiation using nickel or uranium ions, no difference between their fragment distributions can be expected for the same dose level. However, for carbon ions with an intermediate LET, the fragmentation pattern differs from the distribution for very high-LET particles. The results of the model calculations can be used to determine the optimal experimental parameters for a demonstration of the influence of track structure on primary radiation damage. Additionally, we compare the results of our model for two different plasmid geometries.

High LET radiation enhances apoptosis in mutated p53 cancer cells through Caspase-9 activation.

Although mutations in the p53 gene can lead to resistance to radiotherapy, chemotherapy and thermotherapy, high linear energy transfer (LET) radiation induces apoptosis regardless of p53 gene status in cancer cells. The aim of this study was to clarify the mechanisms involved in high LET radiation-induced apoptosis. Human gingival cancer cells (Ca9-22 cells) containing a mutated p53 (mp53) gene were irradiated with X-rays, C-ion (13-100 KeV/microm), or Fe-ion beams (200 KeV/microm). Cellular sensitivities were determined using colony forming assays. Apoptosis was detected and quantified with Hoechst 33342 staining. The activity of Caspase-3 was analyzed with Western blotting and flow cytometry. Cells irradiated with high LET radiation showed a high sensitivity with a high frequency of apoptosis induction. The relative biological effectiveness (RBE) values for the surviving fraction and apoptosis induction increased in a LET-dependent manner. Both RBE curves reached a peak at 100 KeV/microm, and then decreased at values over 100 KeV/microm. When cells were irradiated with high LET radiation, Caspase-3 was cleaved and activated, leading to poly (ADP-ribose) polymerase (PARP) cleavage. In addition, Caspase-9 inhibitor suppressed Caspase-3 activation and apoptosis induction resulting from high LET radiation to a greater extent than Caspase-8 inhibitor. These results suggest that high LET radiation enhances apoptosis by activation of Caspase-3 through Caspase-9, even in the presence of mp53.

Target preparation by the precipitation method for nuclear reactions.

A technique for preparing nuclear reaction targets of various thicknesses was developed by using common filtration technique of hydroxide precipitates with a porous Al(2)O(3) membrane filter. Uniformity was found to be within a few % in each thickness. Durability for beam irradiation was also confirmed. The preparation procedure is convenient and the method is appropriate for several target materials, including not only precious materials but also radioactive materials with low contamination.

Investigating the accuracy of the FLUKA code for transport of therapeutic ion beams in matter.

In-beam positron emission tomography (PET) is currently used for monitoring the dose delivery at the heavy ion therapy facility at GSI Darmstadt. The method is based on the fact that carbon ions produce positron emitting isotopes in fragmentation reactions with the atomic nuclei of the tissue. The relation between dose and beta(+)-activity is not straightforward. Hence it is not possible to infer the delivered dose directly from the PET distribution. To overcome this problem and enable therapy monitoring, beta(+)-distributions are simulated on the basis of the treatment plan and compared with the measured ones. Following the positive clinical impact, it is planned to apply the method at future ion therapy facilities, where beams from protons up to oxygen nuclei will be available. A simulation code capable of handling all these ions and predicting the irradiation-induced beta(+)-activity distributions is desirable. An established and general purpose radiation transport code is preferred. FLUKA is a candidate for such a code. For application to in-beam PET therapy monitoring, the code has to model with high accuracy both the electromagnetic and nuclear interactions responsible for dose deposition and beta(+)-activity production, respectively. In this work, the electromagnetic interaction in FLUKA was adjusted to reproduce the same particle range as from the experimentally validated treatment planning software TRiP, used at GSI. Furthermore, projectile fragmentation spectra in water targets have been studied in comparison to available experimental data. Finally, cross sections for the production of the most abundant fragments have been calculated and compared to values found in the literature.

Wax-impregnated carbon paste electrode modified with mercuric oxalate for the simultaneous determination of heavy metal ions in medicinal plants and Ayurvedic tablets.

A wax-impregnated carbon paste electrode with mercury oxalate as the bulk modifier is found to be suitable for the determination of heavy metal ions by differential pulse anodic stripping voltammetry. The contents of binder and modifier have been optimized, until they showed low background current and easy renewability. The bulk-modified electrode is applied for the simultaneous determination of Zn, Cd, Pb and Cu in medicinal plants and Ayurvedic tablets (Liv 52). The results obtained have been validated with HMDE and AAS and are found to be comparable.

Alterations in gene expression in rat skin exposed to 56Fe ions and dietary vitamin A acetate.

The purpose of the present work was to examine gene expression patterns in rat skin exposed to a beam of (56)Fe ions, a surrogate for the high-energy, heavy-ion galactic radiation background, as a basis for obtaining a better understanding of the possible mechanism(s) behind the radioprotective activity of vitamin A. A 2 x 4-cm rectangle of dorsal rat skin was exposed to 1.01 GeV/nucleon (56)Fe ions generated by the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Gene expression patterns were monitored in either the presence or absence of a 250-ppm dietary supplement of vitamin A acetate in powdered lab chow. Although vitamin A and other retinoids show anti-carcinogenic activity in several animal models, the underlying changes in gene expression have not been examined extensively. At either 1 or 7 day after irradiation, a 1-cm square of irradiated and control rat skin was excised and analyzed using the Affymetrix rat microarray (RG_U34A) system. Microarray responses were displayed and processed by GeneSpring 7.0 and GOTree software. At 1 day after 3 Gy of (56)Fe-ion irradiation, the expression of 110 genes was significantly up-regulated (P < = 0.05) in comparison to levels in control rat skin, while no genes were altered by the vitamin A acetate supplement alone. Combined with (56)Fe-ion radiation, the vitamin A acetate supplement blocked the expression of 88 (80%) of the 110 genes and eliminated 16 of 18 gene categories that were significantly altered (all increased) by the (56)Fe-ion radiation. Categories with large numbers of genes eliminated by the retinoid included response to stress, 33 genes; response to biotic stimulus, 38 genes; signal transduction, 35 genes; and regulation of cellular/physiological process, 40 genes. Even for immune response and response to biotic stimulus, the only two categories that remained significantly altered in the presence of the vitamin, the combined number of altered genes was reduced from 74 to 13. No significant alterations in gene expression were found at 7 days relative to the numbers in controls. The results indicate that at 1 day dietary vitamin A acetate strongly interfered with (56)Fe-ion-induced gene expression within the broad categories of stimulus- and stress-related genes, implying that the latter gene categories likely play a role in the radioprotective action of the vitamin.

Confocal fluorescent imaging of tracks from heavy charged particles utilising new Al2O3:C,Mg crystals.

A completely optical, non-destructive imaging of tracks in a fluorescent crystal provides a new way to detect and to assess doses from heavy charged particles and neutrons. The technique combines confocal fluorescent microscopy with a new radiation-sensitive, luminescent material based on aluminium oxide single crystals doped with carbon, magnesium and having aggregate oxygen vacancy defects (Al2O3:C,Mg). Radiation-induced colour centres in the new material have an absorption band at 620 nm and produce fluorescence at 750 nm with a high quantum yield and a short, 75 +/- 5 ns, fluorescence lifetime. Three-dimensional spatial distribution of fluorescent intensity allows one to obtain depth-dose distributions and to discriminate between high- and low-linear energy transfer radiations. Images of single tracks produced by different types of radiation have been obtained. Irradiations with a calibrated 241Am alpha source showed high efficiency for track detection. Thermal neutrons were detected using a nuclear reaction with a 6LiF radiator and production of alpha particles and tritium ions. Fast neutrons were detected using recoil protons produced in a polyethylene radiator installed in front of the crystalline detector. Three-dimensional reconstruction of a recoil proton propagating through the crystal was demonstrated.