Targeting glutamine dependence with DRP-104 inhibits proliferation and tumor growth of castration-resistant prostate cancer.

BACKGROUND: Prostate cancer (PCa) continues to be one of the leading causes of cancer deaths in men. While androgen deprivation therapy is initially effective, castration-resistant PCa (CRPC) often recurs and has limited treatment options. Our previous study identified glutamine metabolism to be critical for CRPC growth. The glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) blocks both carbon and nitrogen pathways but has dose-limiting toxicity. The prodrug DRP-104 is expected to be preferentially converted to DON in tumor cells to inhibit glutamine utilization with minimal toxicity. However, CRPC cells' susceptibility to DRP-104 remains unclear. METHODS: Human PCa cell lines (LNCaP, LAPC4, C4-2/MDVR, PC-3, 22RV1, NCI-H660) were treated with DRP-104, and effects on proliferation and cell death were assessed. Unbiased metabolic profiling and isotope tracing evaluated the effects of DRP-104 on glutamine pathways. Efficacy of DRP-104 in vivo was evaluated in a mouse xenograft model of neuroendocrine PCa, NCI-H660. RESULTS: DRP-104 inhibited proliferation and induced apoptosis in CRPC cell lines. Metabolite profiling showed decreases in the tricarboxylic acid cycle and nucleotide synthesis metabolites. Glutamine isotope tracing confirmed the blockade of both carbon pathway and nitrogen pathways. DRP-104 treated CRPC cells were rescued by the addition of nucleosides. DRP-104 inhibited neuroendocrine PCa xenograft growth without detectable toxicity. CONCLUSIONS: The prodrug DRP-104 blocks glutamine carbon and nitrogen utilization, thereby inhibiting CRPC growth and inducing apoptosis. Targeting glutamine metabolism pathways with DRP-104 represents a promising therapeutic strategy for CRPC.

Roles of Chloride and Sulfate Ions in Controlling Cadmium Transport in a Soil-Rice System as Evidenced by the Cd Isotope Fingerprint.

Anions accompanying inorganic fertilizers, such as chloride and sulfate ions, potentially affect the solubility, uptake, and transport of Cd to rice grains. However, the role of anions in controlling Cd transport in the soil-soil solution-Fe plaque-rice plant continuum remains poorly understood. Cd isotope ratios were applied to Cd-contaminated soil pots, hydroponic rice, and adsorption experiments with or without KCl and K2SO4 treatments to decipher transport processes in the complex soil-rice system. The chloride and sulfate ions increased the Cd concentrations in the soil solution, Fe plaque, and rice plants. Accordingly, the magnitude of positive fractionation from soil to the soil solution was less pronounced, but that between soil and Fe plaque or rice plant is barely varied. The similar isotope composition of Fe plaque and soil, and the similar fractionation magnitude between Fe plaque and the solution and between goethite and the solution, suggested that desorption-sorption between iron oxides and the solution could be important at the soil-soil solution-Fe plaque continuum. This study reveals the roles of chloride and sulfate ions: (i) induce the mobility of light Cd isotopes from soil to the soil solution, (ii) chloro-Cd and sulfato-Cd complexes contribute to Cd immobilization in the Fe plaque and uptake into roots, and (iii) facilitate second leaves/node II-to-grain Cd transport within shoots. These results provide insights into the anion-induced Cd isotope effect in the soil-rice system and the roles of anions in facilitating Cd migration and transformation.

Effects of dietary starch and ruminally undegraded protein on glucogenic precursors in lactating dairy cows.

Gluconeogenesis is a large contributor to the blood supply of glucose carbons. The impact of varying dietary starch and ruminally degraded protein (RDP) on glucose entry, and the contributions of propionate and lactate to total plasma glucose entry were evaluated. Six cannulated, lactating, Holstein cows were fed one of four treatment diets arranged as a 2 × 2 factorial within a 4 × 4 partially replicated Latin Square design: (1) 8% RDP (LRDP) and 16% starch (LSt), (2) LRDP and 30% starch (HSt), (3) 11% RDP (HRDP) and LSt, or (4) HRDP and HSt. On d 12 of each period, 2-[13C]-sodium propionate (0.15 g/h) was ruminally infused for 4 h; on d 13, 1,2-[13C2]-glucose (0.2 g/h) was infused into the jugular vein for 1 h followed by 1-[13C]-lactate (0.1 g/h) for 1 h. Blood samples were serially collected starting prior to the infusions, and analyzed for plasma glucose, propionate, and lactate isotopic ratios. A one-compartment, glucose carbon model with inputs from lactate, propionate, and other glucogenic precursors (Oth, primarily absorbed glucose plus amino acids) was fitted to the isotope ratio data to derive glucose entry rates and conversion of the precursors to glucose. Milk protein production additively increased when HSt and HRDP were fed (P = 0.05 and P = 0.02, respectively). Plasma glucose and propionate concentrations increased with HSt (P = 0.04 and P = 0.01, respectively) and LRDP (P = 0.02 and P < 0.01, respectively). Total glucose and Oth entry increased (P = 0.03 and P = 0.03, respectively) with HSt, indicating greater glucose absorption from the small intestine or conversion of amino acids to glucose in the liver. However, neither entry rate was affected by RDP. The lack of an RDP effect suggests the increase in microbial outflow in response to RDP did not significantly alter glucose precursor supplies. Entry rates of propionate and lactate carbon to glucose carbon were not affected by treatment suggesting that neither starch nor RDP significantly affected fermentation or lactate production. Derivation of absolute entry rates and contributions to glucose using isotopic tracers is complicated by single carbon removals in the pentose phosphate (PPP), tri-carboxylic acid (TCA), and gluconeogenic pathways, and label randomization with the PPP and TCA pathways. Multiple tracers must be used to avoid assumptions regarding the proportional entries. These results provide insights on glucose supply and contributors, and draw attention to significant label cycling when utilizing isotope techniques.

Zinc Supply Affects Cadmium Uptake and Translocation in the Hyperaccumulator Sedum Plumbizincicola as Evidenced by Isotope Fractionation.

This study employs stable isotope analysis to investigate the mechanisms of cadmium (Cd) and zinc (Zn) interaction in the metal hyperaccumulating plant species Sedum plumbizincicola. To this end, the Cd and Zn isotope compositions of root, stem, leaf, and xylem sap samples were determined during metal uptake and translocation at different Cd and Zn concentrations. The enrichment of light isotopes of both elements in plants during uptake was less pronounced at low metal supply levels, likely reflecting the switch from a low-affinity to a high-affinity transport system at lower levels of external metal supply. The lower δ114/110Cd values of xylem sap when treated with a metabolic inhibitor decreasing the active Cd uptake further supports the preference of heavier Cd isotopes during high-affinity transport. The Δ66Znplant-initial solution or Δ66Znplant-final solution values were similar at different Cd concentrations, indicating negligible interaction of Cd in the Zn uptake process. However, decreasing Zn supply levels significantly increased the enrichment of light Cd isotopes in plants (Δ114/110Cd = -0.08‰) in low-Cd treatments but reduced the enrichment of light Cd isotopes in plants (Δ114/110Cd = 0.08‰) under high Cd conditions. A systematic enrichment of heavy Cd and light Zn isotopes was found in root-to-shoot translocation of the metals. The Cd concentrations of the growth solutions thereby had no significant impact on Zn isotope fractionation during root-to-shoot translocation. However, the Δ114/110Cdtranslocation values hint at possible competition between Cd and Zn for transporters during root-to-shoot transfer and this may impact the transport pathway of Cd. The stable isotope data demonstrate that the interactions between the two metals influenced the uptake and transport mechanisms of Cd in S. plumbizincicola but had little effect on those of Zn.

A unique insight for Xiaoyao San exerts antidepressant effects by modulating hippocampal glucose catabolism using stable isotope-resolved metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) theory, depression is an emotional disease, which is thought to be related to stagnation of liver qi and dysfunction of the spleen in transport. Xiaoyao San (XYS) is considered to have the effects of soothing liver-qi stagnation and invigorating the spleen. The spleen has the function to transport and transform nutrients. The liver has also termed the center of energy metabolism in the body. Therefore, exploring the antidepressant effects of XYS from the perspective of energy metabolism may reveal new findings. AIM OF THE STUDY: Glucose catabolism is an important part of energy metabolism. In recent years, several researchers have found that XYS can exert antidepressant effects by modulating abnormalities in glucose catabolism-related metabolites. The previous research of our research group found that the hippocampus glucose catabolism was disordered in depression. However, the antidepressant potential of XYS through modulating the disorders of hippocampal glucose catabolism and the specific metabolic pathways and targets of XYS action were still unknown. The aim of this study was to address the above scientific questions. MATERIALS AND METHODS: In this research, the CUMS (chronic unpredictable mild stress) model was used as the animal model of depression. The antidepressant effect of XYS was evaluated by behavioral indicators. The specific pathways and targets of XYS modulating the disorders of glucose catabolism in the hippocampus of CUMS rats were obtained by stable isotope-resolved metabolomics. Further, the isotope tracing results were also verified by molecular biology and electron transmission electron microscopy. RESULTS: The results demonstrated that XYS pretreatment could significantly improve the depressive symptoms induced by CUMS. More importantly, it was found that XYS could modulate the disorders of glucose catabolism in the hippocampus of CUMS rats. Stable isotope-resolved metabolomics and enzyme activity tests showed that Lactate dehydrogenase (LDH), Pyruvate carboxylase (PC), and Pyruvate dehydrogenase (PDH) were targets of XYS for modulating the disorders of glucose catabolism in the hippocampus of CUMS rats. The Succinate dehydrogenase (SDH) and mitochondrial respiratory chain complex V (MRCC-Ⅴ) were targets of XYS to improve abnormal mitochondrial oxidative phosphorylation in the hippocampus of CUMS rats. XYS was also found to have the ability to improve the structural damage of mitochondria and nuclei in the hippocampal caused by CUMS. CONCLUSIONS: This study was to explore the antidepressant effect of XYS from the perspective of glucose catabolism based on a strategy combining stable isotope tracing, molecular biology techniques, and transmission electron microscopy. We not only obtained the specific pathways and targets of XYS to improve the disorders of glucose catabolism in the hippocampus of CUMS rats, but also revealed the specific targets of the pathways of XYS compared with VLF.

Antidepressant treatment effects on hippocampal protein turnover: Molecular and spatial insights from mass spectrometry.

A major challenge in managing depression is that antidepressant drugs take a long time to exert their therapeutic effects. For the development of faster-acting treatments, it is crucial to get an improved understanding of the molecular mechanisms underlying antidepressant mode of action. Here, we used a novel mass spectrometry-based workflow to investigate how antidepressant treatment affects brain protein turnover at single-cell and subcellular resolution. We combined stable isotope metabolic labeling, quantitative Tandem Mass Spectrometry (qTMS) and Multi-isotope Imaging Mass Spectrometry (MIMS) to simultaneously quantify and image protein synthesis and turnover in hippocampi of mice treated with the antidepressant paroxetine. We identified changes in turnover of individual hippocampal proteins that reveal altered metabolism-mitochondrial processes and report on subregion-specific turnover patterns upon paroxetine treatment. This workflow can be used to investigate brain protein turnover changes in vivo upon pharmacological interventions at a resolution and precision that has not been possible with other methods to date. Our results reveal acute paroxetine effects on brain protein turnover and shed light on antidepressant mode of action.

Treatment response in dogs with naturally occurring grade 3 elbow osteoarthritis following intra-articular injection of 117mSn (tin) colloid.

The radionuclide 117mSn (tin-117m) embedded in a homogeneous colloid is a novel radiosynoviorthesis (RSO) device for intra-articular (IA) administration to treat synovial inflammation and mitigate osteoarthritis (OA) in dogs. A study to evaluate tin-117m colloid treatment response in dogs with OA was conducted at two centers, the School of Veterinary Medicine at Louisiana State University, and at a referral practice in Houston, Texas. The tin-117m colloid was administered per-protocol to 14 client-owned dogs with radiographically confirmed, grade 3 OA in one or both elbow joints. Dog owners and attending clinicians assessed the level of pain at baseline (BL) and the post-treatment pain response at 90-day intervals for one year. Owners assessed treatment response according to a pain severity score (PSS) and a pain interference score (PIS) as defined by the Canine Brief Pain Inventory. Clinicians reported a lameness score using a 0-5 scale, from no lameness to continuous non-weight bearing lameness, when observing dogs at a walk and a trot. The rate of treatment success as determined by improved mean PSS and PIS scores reported by dog owners was >70% at all time points. Clinicians reported an improved mean pain score from BL at post-treatment Days 90 (p<0.05), 180, and 270. The dog owner and clinician assessments of treatment success were significantly correlated (p>0.05) at Day 90 and Day 180 time points. Results indicated that a single IA dose of tin-117m colloid provided a significant reduction in pain and lameness and improved functionality for up to a full year, with no adverse treatment related effects, in a high percentage of dogs with advanced, clinical OA of the elbow joint.

Tumor Cell-Specific 2'-Fluoro RNA Aptamer Conjugated with Closo-Dodecaborate as A Potential Agent for Boron Neutron Capture Therapy.

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of 10B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying 10B to the tumor cells. This study represents the first example of using 2'-F-RNA aptamer GL44 specific to the human glioblastoma U-87 MG cells as a boron delivery agent for BNCT. The closo-dodecaborate residue was attached to the 5'-end of the aptamer, which was also labeled by the fluorophore at the 3'-end. The resulting bifunctional conjugate showed effective and specific internalization into U-87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neutrons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real-time cell monitoring and the clonogenic test revealed that boron-loaded aptamer decreased specifically the viability of U-87 MG cells to the extent comparable to that of 10B-boronophenylalanine taken as a control. Therefore, we have demonstrated a proof of principle of employing aptamers for targeted delivery of boron-10 isotope in BNCT. Considering their specificity, ease of synthesis, and large toolkit of chemical approaches for high boron-loading, aptamers provide a promising basis for engineering novel BNCT agents.

Magnesium magnetic isotope effects in microbiology.

Two main properties of atomic nuclei-mass and nuclear magnetic moments-are origin of many biological effects. Mass-dependent isotope effects have been studied for a long time. The effect of magnetic isotopes having a magnetic moment and spin was first shown in the early twenty-first century for the magnetic isotope magnesium 25Mg on enzymatic ATP synthesis. This stimulated the search for experimental evidence and theoretical justification of magnetic nuclei influence on biological processes. This review contains the results of scientific research on the magnesium magnetic isotope effects in microbiology. Microorganisms have been found to be sensitive to the presence of nuclear magnetic moment of magnesium isotope 25Mg compared with non-magnetic 24,26Mg isotopes.

Exploring the mechanism of olfactory recognition in the initial stage by modeling the emission spectrum of electron transfer.

Olfactory sense remains elusive regarding the primary reception mechanism. Some studies suggest that olfaction is a spectral sense, the olfactory event is triggered by electron transfer (ET) across the odorants at the active sites of odorant receptors (ORs). Herein we present a Donor-Bridge-Acceptor model, proposing that the ET process can be viewed as an electron hopping from the donor molecule to the odorant molecule (Bridge), then hopping off to the acceptor molecule, making the electronic state of the odorant molecule change along with vibrations (vibronic transition). The odorant specific parameter, Huang-Rhys factor can be derived from ab initio calculations, which make the simulation of ET spectra achievable. In this study, we revealed that the emission spectra (after Gaussian convolution) can be acted as odor characteristic spectra. Using the emission spectrum of ET, we were able to reasonably interpret the similar bitter-almond odors among hydrogen cyanide, benzaldehyde and nitrobenzene. In terms of isotope effects, we succeeded in explaining why subjects can easily distinguish cyclopentadecanone from its fully deuterated analogue cyclopentadecanone-d28 but not distinguishing acetophenone from acetophenone-d8.

Stabilizing Antibody Cocktails for Mass Cytometry.

Mass cytometry is increasingly employed in larger immune profiling studies involving data acquisitions across several days and multiple sites. For gaining a maximum of information from respective data by computational analyses, several techniques have been developed to minimize noise in mass cytometric data sets, such as sample banking, standardized instrument setup, sample barcoding, and signal normalization. However, the repeated preparation of cocktails composed of isotope-tagged antibodies remained a significant source of error. We here show that premixed antibody cocktails fail to deliver expected staining patterns when stored at 4°C for 4 weeks. As a solution, we developed and tested a cryopreservation method for highly multiplexed antibody cocktails for mass cytometry including lanthanide, palladium, and platinum conjugates that yielded stable staining patterns for at least 9 months when stored at temperatures below -80°C. Using frozen aliquots of antibody cocktails is an economic and flexible approach to significantly improve data consistency in large mass cytometry studies with repetitive staining/measurement cycles spanning several days or involving multiple data acquisition sites. © 2019 International Society for Advancement of Cytometry.

Magnetic Fields and Magnetic Isotope 25Mg Effects on Biofilms Formation by Bacteria E. coli.

The biofilm formation by bacteria E. coli is a magnetosensitive process. The combined effects of a magnetic magnesium isotope 25Mg and a static magnetic field in the range of 20-35 mT stimulate biofilm formation by E. coli compared to nonmagnetic magnesium isotopes 24.26Mg. Magnetic field effects in the range of 2-10 mT, recorded for all bacteria regardless of the magnesium-isotope enrichment of the nutrient medium, indicate the sensitivity of intracellular processes to weak magnetic fields.

The Use of Stable Isotopic Tracers in Metallomics Studies.

Mass spectrometry represents an essential technique in Metallomics studies. It permits the identification of metal-containing molecules as part of the metallome as well as their quantification at low concentration levels. The technique becomes even more powerful in combination with the use of isotopically enriched species. Provided that they are stable, these isotopically labelled species can be easily distinguished from their natural counterparts by mass spectrometric techniques. This capability permits that these species are used for accurate and precise quantitative experiments and/or metabolic studies applying inductively coupled plasma as ionization source. In this chapter, we present the different concepts of using stable isotope tracers and isotope dilution analysis as quantification strategy. Besides some fundamental aspects, various examples from Metallomics studies, for instance, on the preparation of isotopically enriched metalloproteins and determination by isotope dilution analysis or the exploration of the biological pathways of Se species, are shown in order to demonstrate the usefulness of isotopes.

Magnetosensitivity of bacteria E. coli: Magnetic isotope and magnetic field effects.

The biological effects of a 25 Mg nuclear spin and weak magnetic fields have been found and studied by using bacterial cells of Escherichia coli (E. coli) grown on standard M9 nutrient media with different isotopes of magnesium: 24 Mg, 25 Mg, 26 Mg, and a natural mixture of Mg isotopes. Among these isotopes only 25 Mg has a nuclear spin I = 5/2 and nuclear magnetic moment which have been known to affect enzymatic processes in vitro due to hyperfine interactions with uncoupled electrons of substrates. Other non-magnetic magnesium isotopes, 24 Mg and 26 Mg, have neither a nuclear spin (I = 0) nor a nuclear magnetic moment. Bacterial cells grown on 25 Mg-media and enriched with this isotope manifest a higher growth rate and colony-forming units (CFU) compared with cells grown on media containing nonmagnetic 24 Mg and 26 Mg isotopes. Magnetic field dependencies of CFU cells enriched with different magnesium isotopes have been obtained. The observed isotope-dependent differences are explained by intracellular enzymatic ion-radical reactions which are magnetic field and nuclear spin sensitive. Enzymatic synthesis of ATP is considered as the most probable magnetosensitive biochemical process in vivo as far as effectiveness of ATP production is concerned; it determines the viability of cells and was shown in vitro as a nuclear spin-dependent reaction. Bioelectromagnetics. 38:581-591, 2017. © 2017 Wiley Periodicals, Inc.

Hyperpolarized helium-3 magnetic resonance lung imaging of non-sedated infants and young children: a proof-of-concept study.

PURPOSE: To develop and evaluate a protocol for hyperpolarized helium-3 (HHe) ventilation magnetic resonance imaging (MRI) of the lungs of non-sedated infants and children. MATERIALS AND METHODS: HHe ventilation MRI was performed on seven children ≤4years old. Contiguous 2D-spiral helium-3 images were acquired sequentially with a scan time of ≤0.2s/slice. RESULTS: Motion-artifact-free, high signal-to-noise ratio (SNR) images of lung ventilation were obtained. Gas was homogeneously distributed in healthy individuals; focal ventilation defects were found in patients with respiratory diseases. CONCLUSION: HHe ventilation MRI can aid assessment of pediatric lung disease even at a young age.

Use of hyperpolarized helium-3 MRI to assess response to ivacaftor treatment in patients with cystic fibrosis.

BACKGROUND: This pilot study evaluated the effect of short- and long-term ivacaftor treatment on hyperpolarized 3He-magnetic resonance imaging (MRI)-defined ventilation defects in patients with cystic fibrosis aged ≥12years with a G551D-CFTR mutation. METHODS: Part A (single-blind) comprised 4weeks of ivacaftor treatment; Part B (open-label) comprised 48weeks of treatment. The primary outcome was change from baseline in total ventilation defect (TVD; total defect volume:total lung volume ratio). RESULTS: Mean change in TVD ranged from -8.2% (p=0.0547) to -12.8% (p=0.0078) in Part A (n=8) and -6.3% (p=0.1953) to -9.0% (p=0.0547) in Part B (n=8) as assessed by human reader and computer algorithm, respectively. CONCLUSIONS: TVD responded to ivacaftor therapy. 3He-MRI provides an individual quantification of disease burden that may be able to detect aspects of the disease missed by population-based spirometry metrics. Assessments by human reader and computer algorithm exhibit similar trends, but the latter appears more sensitive. www.clinicaltrials.gov identifier: NCT01161537.

An optimized method for measuring fatty acids and cholesterol in stable isotope-labeled cells.

Stable isotope labeling has become an important methodology for determining lipid metabolic parameters of normal and neoplastic cells. Conventional methods for fatty acid and cholesterol analysis have one or more issues that limit their utility for in vitro stable isotope-labeling studies. To address this, we developed a method optimized for measuring both fatty acids and cholesterol from small numbers of stable isotope-labeled cultured cells. We demonstrate quantitative derivatization and extraction of fatty acids from a wide range of lipid classes using this approach. Importantly, cholesterol is also recovered, albeit at a modestly lower yield, affording the opportunity to quantitate both cholesterol and fatty acids from the same sample. Although we find that background contamination can interfere with quantitation of certain fatty acids in low amounts of starting material, our data indicate that this optimized method can be used to accurately measure mass isotopomer distributions for cholesterol and many fatty acids isolated from small numbers of cultured cells. Application of this method will facilitate acquisition of lipid parameters required for quantifying flux and provide a better understanding of how lipid metabolism influences cellular function.

Can heavy isotopes increase lifespan? Studies of relative abundance in various organisms reveal chemical perspectives on aging.

Stable heavy isotopes co-exist with their lighter counterparts in all elements commonly found in biology. These heavy isotopes represent a low natural abundance in isotopic composition but impose great retardation effects in chemical reactions because of kinetic isotopic effects (KIEs). Previous isotope analyses have recorded pervasive enrichment or depletion of heavy isotopes in various organisms, strongly supporting the capability of biological systems to distinguish different isotopes. This capability has recently been found to lead to general decline of heavy isotopes in metabolites during yeast aging. Conversely, supplementing heavy isotopes in growth medium promotes longevity. Whether this observation prevails in other organisms is not known, but it potentially bears promise in promoting human longevity.

[Impact of neutron radiation on the viability of tumor cells cultured in the presence of boron-10 isotope].

Objective: To investigate the impact of a neutron beam formed with the accelerator-based epithermal neutron source designed at the G.I. Budker Institute of Nuclear Physics (INP) on the viability of human and animal tumor cells cultured in the presence of boron-10 isotope. Material and Methods: Human U251 and T98G glioma cells and Chinese hamster CHO-K1 and V-79 cells were incubated at various concentrations in the culture medium containing 10B-enriched L-boronophenylalanine. The cells were irradiated with a neuron beam using the accelerator-based epithermal neuron source. A clonogenic assay was used to evaluate the viability of the irradiated cells. The absorbed doses obtained from elastic scattering of fast neutrons by substance nuclei and the doses obtained from boron neutron capture were calculated using the NMS code. The absorbed doses of gamma-radiation were measured with a mixed radiation dosimeter. Results: The viability of boron-containing and intact human U251 and T98G cell lines and Chinese hamster CHO-K1 and V-79 cells was analyzed after neutron beam radiation. Irradiation of all four cell lines were cultured in the presence of 10B was shown to reduce their colony-forming capacity compared with the control. Elevated boron levels in the culture medium resulted in a significant decrease in the proportion of survived cells. Radiation had the most pronounced impact on the proliferative capacity of the human U251 glioma cell lines. Conclusion: The cultures of human tumor cells and mammalian cells demonstrated that the neutron beam formed with the accelerator-based epithermal neutron source designed at the INP, was effective in reducing the viability of tumor cells in the presence of 10B.