Exploring the nanoscale: AFM-IR visualization of cysteine adsorption on gold nanoparticles.

This study focuses on the adsorption process of L-cysteine (Cys), a sulfur-containing amino acid, onto monolayers of gold nanoparticles (AuNPs) prepared through distinct protocols on mica substrates. Two types of AuNPs were prepared using two different methods: the first employed a physical approach, which combined the Inert Gas Condensation (IGC) technique with the magnetron sputtering method, while the second utilized a chemical method involving the reduction of tetrachloroauric acid with trisodium citrate (TC). The characterization of AuNPs was performed using transmission electron microscopy (TEM) and atomic force microscopy (AFM), of up to 5 ± 1.3 nm for bare AuNPs obtained through vacuum techniques, and up to 12 ± 5 nm for negatively charged, citrate-stabilized TCAuNPs(-). The application of spectroscopic techniques based on the surface-enhanced effects allows for describing the adsorption process in both micro- and nanoscale systems: Cys/bare AuNPs and Cys/ TCAuNPs(-). The commonly used surface-enhanced Raman spectroscopy (SERS) technique provided insights into adsorption behaviours at the microscale level. In the case of TCAuNPs(-), an interaction involving the lone electron pair of sulfur (S) atom and metal surface, while on the bare AuNPs, S is adsorbed on the surface, but the cleavage of the SH group is not discernible. Nanoscale analysis was complemented using AFM combined with the surface-enhanced infrared absorption spectroscopy (AFM-SEIRA) technique. AFM-SEIRA map indicated the formation of hot spot which were predominantly located between aggregated TCAuNPs(-) and on specific NPs surfaces (area between NPs and gold-coated tip). Results from the SERS and AFM-SEIRA techniques were in good agreement, underscoring the comprehensive understanding achieved through the chosen experimental approach regarding the Cys interactions with layers of AuNPs.

Synthesis of Manganese Zinc Ferrite Nanoparticles in Medical-Grade Silicone for MRI Applications.

The aim of this project is to fabricate hydrogen-rich silicone doped with magnetic nanoparticles for use as a temperature change indicator in magnetic resonance imaging-guided (MRIg) thermal ablations. To avoid clustering, the particles of mixed MnZn ferrite were synthesized directly in a medical-grade silicone polymer solution. The particles were characterized by transmission electron microscopy, powder X-ray diffraction, soft X-ray absorption spectroscopy, vibrating sample magnetometry, temperature-dependent nuclear magnetic resonance relaxometry (20 °C to 60 °C, at 3.0 T), and magnetic resonance imaging (at 3.0 T). Synthesized nanoparticles were the size of 4.4 nm ± 2.1 nm and exhibited superparamagnetic behavior. Bulk silicone material showed a good shape stability within the study's temperature range. Embedded nanoparticles did not influence spin-lattice relaxation, but they shorten the longer component of spin-spin nuclear relaxation times of silicone's protons. However, these protons exhibited an extremely high r2* relaxivity (above 1200 L s-1 mmol-1) due to the presence of particles, with a moderate decrease in the magnetization with temperature. With an increased temperature decrease of r2*, this ferro-silicone can be potentially used as a temperature indicator in high-temperature MRIg ablations (40 °C to 60 °C).

In Vivo Supportive Effects of Mesenchymal Stem Cells on Fat Graft Stabilization and Local Induction of Angiogenesis Are Not Dependent on the Cell Donor Age or In Vitro Cell Culture Duration.

Mesenchymal stromal cells from adipose tissue (adipose stromal cells, ASCs) are regulators of repair processes in situ by paracrine mechanisms. These unique capabilities make ASCs candidates for the regenerative medicine applications, including cell-assisted lipotransfer method. ASC aging processes have been extensively researched in vitro, there is however limited information about the impact of ASC aging on their biological role in tissue regeneration in vivo. The aim of our study was the research of the possible effects of aging processes of ASCs resulting from the donor age or from in vitro aging during long-term culture (ASC expansion in bioreactors) on their capability to support survival of adipose subcutaneous transplants in rats. The supportive in vivo effects of ASCs from young donors were compared with the effects of ASCs from old donors and ASCs "aged" in long-term in vitro cultures. Fat grafts enriched with ASCs (regardless of their age) retain their volume longer than fat grafts without ASCs supplementation. Vascular expansion in cell-enriched fat grafts was more intense when compared with the controls. It may be concluded that the aging of ASCs does not substantially reduce their ability for the support of the survival of adipose tissue grafts.

The influence of IONPs core size on their biocompatibility and activity in in vitro cellular models.

Although the key factor affecting the biocompatibility of IONPs is the core size, there is a lack of regular investigation concerning the impact of the parameter on the toxicity of these nanomaterials. Therefore, such studies were carried out in this paper. Their purpose was to compare the influence of PEG-coated-magnetite NPs with the core of 5, 10 and 30 nm on six carefully selected cell lines. The proliferation rate, viability, metabolic activity, migration activity, ROS levels and cytoskeleton architecture of cells have been evaluated for specified incubation periods. These were 24 and 72-h long incubations with IONPs administered in two doses: 5 and 25 µg Fe/ml. A decrease in viability was observed after exposure to the tested NPs for all the analyzed cell lines. This effect was not connected with core diameter but depended on the exposure time to the nanomaterials. IONPs increased not only the proliferation rate of macrophages-being phagocytic cells-but also, under certain conditions stimulated tumor cell divisions. Most likely, the increase in proliferation rate of macrophages contributed to the changes in the architecture of their cytoskeleton. The growth in the level of ROS in cells had been induced mainly by the smallest NPs. This effect was observed for HEK293T cells and two cancerous lines: U87MG (at both doses tested) and T98G (only for the higher dose). This requires further study concerning both potential toxicity of such IONPs to the kidneys and assessing their therapeutic potential in the treatment of glioblastoma multiforme.

Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies.

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase-associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition-induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies. SIGNIFICANCE: These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.

Silver Nanoparticles as a Tool for the Study of Spontaneous Aggregation of Immunoglobulin Monoclonal Free Light Chains.

Some misfolded proteins, e.g., immunoglobulin monoclonal free light chains (FLC), tend to form fibrils. Protein deposits in tissue may lead to amyloidosis and dysfunction of different organs. There is currently no technique allowing for the identification of FLC that are prone to aggregate. The development of such a method would enable the early selection of patients at high risk of developing amyloidosis. The aim of this study was to investigate whether silver nanoparticles (AgNPs) could be a useful tool to study the process of aggregation of FLC and their susceptibility to form the protein deposits. Mixtures of AgNPs and urine samples from patients with multiple myeloma were prepared. To evaluate the aggregation process of nanoparticles coated with proteins, UV-visible spectroscopy, transmission electron microscopy, and the original laser light scattering method were used. It has been shown that some clones of FLC spontaneously triggered aggregation of the nanoparticles, while in the presence of others, the nanoparticle solution became hyperstable. This is probably due to the structure of the chains themselves, unique protein-AgNPs interactions and perhaps correlates with the tendency of some FLC clones to form deposits. Nanoparticle technology has proven to be helpful in identifying clones of immunoglobulin FLC that tend to aggregate.

Cytotoxic Efficacy and Resistance Mechanism of a TRAIL and VEGFA-Peptide Fusion Protein in Colorectal Cancer Models.

TNF-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein capable of selectively inducing apoptosis in cancer cells by binding to its cognate receptors. Here, we examined the anticancer efficacy of a recently developed chimeric AD-O51.4 protein, a TRAIL fused to the VEGFA-originating peptide. We tested AD-O51.4 protein activity against human colorectal cancer (CRC) models and investigated the resistance mechanism in the non-responsive CRC models. The quantitative comparison of apoptotic activity between AD-O51.4 and the native TRAIL in nine human colorectal cancer cell lines revealed dose-dependent toxicity in seven of them; the immunofluorescence-captured receptor abundance correlated with the extent of apoptosis. AD-O51.4 reduced the growth of CRC patient-derived xenografts (PDXs) with good efficacy. Cell lines that acquired AD-O51.4 resistance showed a significant decrease in surface TRAIL receptor expression and apoptosis-related proteins, including Caspase-8, HSP60, and p53. These results demonstrate the effectiveness of AD-O51.4 protein in CRC preclinical models and identify the potential mechanism underlying acquired resistance. Progression of AD-O51.4 to clinical trials is expected.

Synthesis of Co-Fe 1D Nanocone Array Electrodes Using Aluminum Oxide Template.

Porous anodic alumina oxide (AAO) obtained via two-step anodization is a material commonly used as a template for fabricating 1D nanostructures. In this work, copper and cobalt-iron 1D nanocones were obtained by an electrodeposition method using AAO templates. The templates were produced using two-step anodization in H2C2O4. The Co-Fe nanostructures are characterized by homogeneous pore distribution. The electrocatalytic activity of the produced nanomaterials was determined in 1 M NaOH using the linear sweep voltammetry (LSV) and chronopotentiometry (CP) methods. These materials can be used as catalysts in the water-splitting reaction. The sample's active surface area was calculated and compared with bulk materials.

Silver Nanoparticle-Based Assay for the Detection of Immunoglobulin Free Light Chains.

There is a wide spectrum of malignant diseases that are connected with the clonal proliferation of plasma cells, which cause the production of complete immunoglobulins or their fragments (heavy or light immunoglobulin chains). These proteins may accumulate in tissues, leading to end organ damage. The quantitative determination of immunoglobulin free light chains (FLCs) is considered to be the gold standard in the detection and treatment of multiple myeloma (MM) and amyloid light-chain (AL) amyloidosis. In this study, a silver nanoparticle-based diagnostic tool for the quantitation of FLCs is presented. The optimal test conditions were achieved when a metal nanoparticle (MNP) was covered with 10 particles of an antibody and conjugated by 5-50 protein antigen particles (FLCs). The formation of the second antigen protein corona was accompanied by noticeable changes in the surface plasmon resonance spectra of the silver nanoparticles (AgNPs), which coincided with an increase of the hydrodynamic diameter and increase in the zeta potential, as demonstrated by dynamic light scattering (DLS). A decrease of repulsion forces and the formation of antigen-antibody bridges resulted in the agglutination of AgNPs, as demonstrated by transmission electron microscopy and the direct formation of AgNP aggregates. Antigen-conjugated AgNPs clusters were also found by direct observation using green laser light scattering. The parameters of the specific immunochemical aggregation process consistent with the sizes of AgNPs and the protein particles that coat them were confirmed by four physical methods, yielding complementary data concerning a clinically useful AgNPs aggregation test.

Polypyrrole⁻Nickel Hydroxide Hybrid Nanowires as Future Materials for Energy Storage.

Hybrid materials play an essential role in the development of the energy storage technologies since a multi-constituent system merges the properties of the individual components. Apart from new features and enhanced performance, such an approach quite often allows the drawbacks of single components to be diminished or reduced entirely. The goal of this paper was to prepare and characterize polymer-metal hydroxide (polypyrrole-nickel hydroxide, PPy-Ni(OH)2) nanowire arrays demonstrating good electrochemical performance. Nanowires were fabricated by potential pulse electrodeposition of pyrrole and nickel hydroxide into nanoporous anodic alumina oxide (AAO) template. The structural features of as-obtained PPy-Ni(OH)2 hybrid nanowires were characterized using FE-SEM and TEM analysis. Their chemical composition was confirmed by energy-dispersive x-ray spectroscopy (EDS). The presence of nickel hydroxide in the synthesized PPy-Ni(OH)2 nanowire array was investigated by X-ray photoelectron spectroscopy (XPS). Both FE-SEM and TEM analyses confirmed that the obtained nanowires were composed of a polymer matrix with nanoparticles dispersed within. EDS and XPS techniques confirmed the presence of PPy-Ni(OH)2 in the nanowire array obtained. Optimal working potential range (i.e., available potential window), charge propagation, and cyclic stability of the electrodes were determined with cyclic voltammetry (CV) at various scan rates. Interestingly, the electrochemical stability window for the aqueous electrolyte at PPy-Ni(OH)2 nanowire array electrode was remarkably wider (ca. 2 times) in comparison with the non-modified PPy electrode. The capacitance values, calculated from cyclic voltammetry performed at 20 mV s-1, were 25 F cm-2 for PPy and 75 F cm-2 for PPy-Ni(OH)2 array electrodes. The cyclic stability of the PPy nanowire array electrode up to 100 cycles showed a capacitance fade of about 13%.

Tuning of the Seebeck Coefficient and the Electrical and Thermal Conductivity of Hybrid Materials Based on Polypyrrole and Bismuth Nanowires.

The growing demand for clean energy catalyzes the development of new devices capable of generating electricity from renewable energy resources. One of the possible approaches focuses on the use of thermoelectric materials (TE), which may utilize waste heat, water, and solar thermal energy to generate electrical power. An improvement of the performance of such devices may be achieved through the development of composites made of an organic matrix filled with nanostructured thermoelectric materials working in a synergetic way. The first step towards such designs requires a better understanding of the fundamental interactions between available materials. In this paper, this matter is investigated and the questions regarding the change of electrical and thermal properties of nanocomposites based on low-conductive polypyrrole enriched with bismuth nanowires of well-defined geometry and morphology is answered. It is clearly demonstrated that the electrical conductivity and the Seebeck coefficient may be tuned either simultaneously or separately within particular Bi NWs content ranges, and that both parameters may be increased at the same time.

Challenges in Stratifying the Molecular Variability of Patient-Derived Colon Tumor Xenografts.

Colorectal cancer (CRC) is the second most common cancer in Europe and a leading cause of death worldwide. Patient-derived xenograft (PDX) models maintain complex intratumoral biology and heterogeneity and therefore remain the platform of choice for translational drug discovery. In this study, we implanted 37 primary CRC tumors and five CRC cell lines into NU/J mice to develop xenograft models. Primary tumors and established xenografts were histologically assessed and surveyed for genetic variants and gene expression using a panel of 409 cancer-related genes and RNA-seq, respectively. More than half of CRC tumors (20 out of 37, 54%) developed into a PDX. Histological assessment confirmed that PDX grading, stromal components, inflammation, and budding were consistent with those of the primary tumors. DNA sequencing identified an average of 0.14 variants per gene per sample. The percentage of mutated variants in PDXs increased with successive passages, indicating a decrease in clonal heterogeneity. Gene Ontology analyses of 4180 differentially expressed transcripts (adj. p value < 0.05) revealed overrepresentation of genes involved in cell division and catabolic processes among the transcripts upregulated in PDXs; downregulated transcripts were associated with GO terms related to extracellular matrix organization, immune responses, and angiogenesis. Neither a transcriptome-based consensus molecular subtype (CMS) classifier nor three other predictors reliably matched PDX molecular subtypes with those of the primary tumors. In sum, both genetic and transcriptomic profiles differed between donor tumors and PDXs, likely as a consequence of subclonal evolution at the early phase of xenograft development, making molecular stratification of PDXs challenging.

Formation and stability of manganese-doped ZnS quantum dot monolayers determined by QCM-D and streaming potential measurements.

Manganese-doped ZnS quantum dots (QDs) stabilized by cysteamine hydrochloride were successfully synthesized. Their thorough physicochemical characteristics were acquired using UV-Vis absorption and photoluminescence spectroscopy, X-ray diffraction, dynamic light scattering (DLS), transmission electron microscopy (HR-TEM), energy dispersive spectroscopy (EDS) and Fourier transform infrared (FT-IR) spectroscopy. The average particle size, derived from HR-TEM, was 3.1nm, which agrees with the hydrodynamic diameter acquired by DLS, that was equal to 3-4nm, depending on ionic strength. The quantum dots also exhibited a large positive zeta potential varying between 75 and 36mV for ionic strength of 10-4 and 10-2M, respectively (at pH 6.2) and an intense luminescent emission at 590nm. The quantum yield was equal to 31% and the optical band gap energy was equal to 4.26eV. The kinetics of QD monolayer formation on silica substrates (silica sensors and oxidized silicon wafers) under convection-controlled transport was quantitatively evaluated by the quartz crystal microbalance (QCM) and the streaming potential measurements. A high stability of the monolayer for ionic strength 10-4 and 10-2M was confirmed in these measurements. The experimental data were adequately reflected by the extended random sequential adsorption model (eRSA). Additionally, thorough electrokinetic characteristics of the QD monolayers and their stability for various ionic strengths and pH were acquired by streaming potential measurements carried out under in situ conditions. These results were quantitatively interpreted in terms of the three-dimensional (3D) electrokinetic model that furnished bulk zeta potential of particles for high ionic strengths that is impractical by other experimental techniques. It is concluded that these results can be used for designing of biosensors of controlled monolayer structure capable to bind various ligands via covalent as well as electrostatic interactions.

Nanocrystalline TiO2/SnO2 heterostructures for gas sensing.

The aim of this research is to study the role of nanocrystalline TiO2/SnO2 n-n heterojunctions for hydrogen sensing. Nanopowders of pure SnO2, 90 mol % SnO2/10 mol % TiO2, 10 mol % SnO2/90 mol % TiO2 and pure TiO2 have been obtained using flame spray synthesis (FSS). The samples have been characterized by BET, XRD, SEM, HR-TEM, Mössbauer effect and impedance spectroscopy. Gas-sensing experiments have been performed for H2 concentrations of 1-3000 ppm at 200-400 °C. The nanomaterials are well-crystallized, anatase TiO2, rutile TiO2 and cassiterite SnO2 polymorphic forms are present depending on the chemical composition of the powders. The crystallite sizes from XRD peak analysis are within the range of 3-27 nm. Tin exhibits only the oxidation state 4+. The H2 detection threshold for the studied TiO2/SnO2 heterostructures is lower than 1 ppm especially in the case of SnO2-rich samples. The recovery time of SnO2-based heterostructures, despite their large responses over the whole measuring range, is much longer than that of TiO2-rich samples at higher H2 flows. TiO2/SnO2 heterostructures can be intentionally modified for the improved H2 detection within both the small (1-50 ppm) and the large (50-3000 ppm) concentration range. The temperature Tmax at which the semiconducting behavior begins to prevail upon water desorption/oxygen adsorption depends on the TiO2/SnO2 composition. The electrical resistance of sensing materials exhibits a power-law dependence on the H2 partial pressure. This allows us to draw a conclusion about the first step in the gas sensing mechanism related to the adsorption of oxygen ions at the surface of nanomaterials.

Tissue response after implantation of pure titanium and bioresorbable screws in scapula with postoperative irradiation: an experimental study on rats.

OBJECTIVE: The study focuses on the comparison of tissue reaction to titanium and bioresorbable implants with and without postoperative irradiation on an animal model. MATERIALS AND METHODS: Thirty-nine LEW/W rats were randomly assigned to experimental or control groups. One titanium and one bioresorbable screw (poly-L-lactide [PLLA] and L- and D-lactide poly-L/D-lactide [PDLLA]) were implanted into the left scapulas of 24 rats. Half of them received 30 Gy to the operation site and the other half received 42 Gy. In the control groups, 3 rats received 30 Gy, and 6 rats received 42 Gy to the scapula area without operation; and 6 rats had implants inserted as in the experimental group, but received no postoperative irradiation. The scapulas were removed 14 or 30 days after irradiation and a histologic analysis was performed. RESULTS: The host tissue reaction to titanium and PLLA-PDLLA screws without postoperative irradiation was of similar intensity. In irradiated animals, the inflammatory tissue reaction was more evident around the titanium screws than around the bioresorbable screws, irrespective of the radiation dose and of the time that elapsed from the irradiation. The reaction was more evident on the 14th day than on the 30th day after the last radiation dose (70 and 86 days after surgery, respectively). The intensity of the inflammatory tissue reaction, irrespective of the implant type, was more intense in the group irradiated with 42 Gy. CONCLUSIONS: PLLA-PDLLA implants appear to cause less tissue reaction after irradiation and could be safer reconstructive devices than titanium implants for patients undergoing surgery and adjuvant radiotherapy for cancer.

The N-reductive system composed of mitochondrial amidoxime reducing component (mARC), cytochrome b5 (CYB5B) and cytochrome b5 reductase (CYB5R) is regulated by fasting and high fat diet in mice.

The mitochondrial amidoxime reducing component mARC is the fourth mammalian molybdenum enzyme. The protein is capable of reducing N-oxygenated structures, but requires cytochrome b5 and cytochrome b5 reductase for electron transfer to catalyze such reactions. It is well accepted that the enzyme is involved in N-reductive drug metabolism such as the activation of amidoxime prodrugs. However, the endogenous function of the protein is not fully understood. Among other functions, an involvement in lipogenesis is discussed. To study the potential involvement of the protein in energy metabolism, we tested whether the mARC protein and its partners are regulated due to fasting and high fat diet in mice. We used qRT-PCR for expression studies, Western Blot analysis to study protein levels and an N-reductive biotransformation assay to gain activity data. Indeed all proteins of the N-reductive system are regulated by fasting and its activity decreases. To study the potential impact of these changes on prodrug activation in vivo, another mice experiment was conducted. Model compound benzamidoxime was injected to mice that underwent fasting and the resulting metabolite of the N-reductive reaction, benzamidine, was determined. Albeit altered in vitro activity, no changes in the metabolite concentration in vivo were detectable and we can dispel concerns that fasting alters prodrug activation in animal models. With respect to high fat diet, changes in the mARC proteins occur that result in increased N-reductive activity. With this study we provide further evidence that the endogenous function of the mARC protein is linked with lipid metabolism.

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

Susceptibility loci and chromosomal abnormalities in radiation induced hematopoietic neoplasms in mice.

Genetics of susceptibility to radiation-induced hematopoietic neoplasms and somatic chromosomal aberrations were analyzed in 305 backcross (CcS-17xCcS-2)xCcS-2 mice of two CcS/Dem recombinant congenic strains. Irradiated CcS-2 mice were previously shown to exhibit high frequency of myeloid neoplasms whereas irradiated CcS-17 mice were susceptible to T-cell lymphomas. Mice were exposed to four whole-body irradiation doses of 1.7 Gy at one week intervals, which resulted in 139 hematopoietic neoplasms. The hematopoietic neoplasms were classified according to the Bethesda proposals for classification of lymphoid and nonlymphoid hematopoietic neoplasms in mice. Genotyping of mice with 24 microsatellite markers and subsequent statistical analysis indicated linkage of the radiation induced T-lymphomas to two loci on chromosome 10 (D10Mit134) and chromosome 12 (D12Mit52). T-lymphoma susceptibility appeared to be linked to D10Mit134 in a sex dependent way. In contrast, the myeloid-granulocytic leukemias susceptibility is linked to combined effects of chromosome 5 (D5Mit179) and 16 (D16Mit34). Cytogenetic analysis was performed according to the standard G-bands procedure and confirmed using FISH method. We found non-random numerical and structural chromosomal changes in lymphoid neoplasms. Cytogenetic analysis indicated chromosomal aberrations presumably associated with lymphomagenesis, no specific cancer-related rearrangements were observed.