Consumption of Apigenin Prevents Radiation-induced Gut Dysbiosis in Male C57BL/6J Mice Exposed to Silicon Ions.

The search for medical treatments to prevent radiation-induced damage to gastrointestinal tissue is crucial as such injuries can be fatal. This study aimed to investigate the effects of apigenin (AP) on the gut microbiome of irradiated mice, as it is a promising radiation countermeasure. Male C57BL/6J mice were divided into four groups, with six mice in each group. Two groups were given food with apigenin (20 mg/kg body weight or AP 20) before and after exposure to 0 or 50 cGy of silicon (28Si) ions, while another two groups of mice received regular diet without apigenin (0 mg/kg body weight or AP 0) before and after irradiation. The duodenum, the primary site for oral AP absorption, was collected from each mouse seven days after radiation exposure. Using 16S rRNA amplicon sequencing, we found significant differences in microbial diversity among groups. Firmicutes and Bacteroidetes were the major phyla for all groups, while actinobacterial and proteobacterial sequences represented only a small percentage. Mice not given dietary apigenin had a higher Firmicutes and Bacteroidetes (F/B) ratio and an imbalanced duodenal microbiota after exposure to radiation, while irradiated mice given apigenin had maintained homeostasis of the microbiota. Additionally, irradiated mice not given apigenin had decreased probiotic bacteria abundance and increased inflammation, while apigenin-supplemented mice had reduced inflammation and restored normal histological structure. In conclusion, our results demonstrate the potential of dietary apigenin as a countermeasure against radiation-induced gut injuries due to its anti-inflammatory activity, reduction of gut microbiota dysbiosis, and increase in probiotic bacteria (e.g., Lachnospiraceae, Muribaculaceae and Bifidobacteriaceae).

[Autoimmune/inflammatory syndrome induced by aduvants].

For decades, breast implants have been available for breast reconstructions and breast augmentations to improve the patients' health-related quality of life. Silicone implants (SI) have been used since the middle of the last century for breast reconstruction, for example after breast cancer, for birth defects, gender confirmation procedures, or for breast augmentation. Every year, several hundred SI are performed in Iceland for these purposes, but no central register is maintained. It can be estimated that at least 1000 - 3000 women have SI in Iceland and that around 300 Icelandic patients get SI every year. This informal review article discusses the so-called ASIA syndrome, the immunological effects of silicone and the possible relationship of SI to autoimmune diseases, symptoms, and diagnosis. In the methodology, this paper does not rely on the strict conditions of systematic reviews, but the authors relied only on peer-reviewed sources through PubMed, UpToDate and Scopus. The keywords used are silicon, silicon implant, silicon particles, immune response, autoimmunity, autoinflammation, Autoimmune/inflammatory syndrome induced by aduvants, ASIA, ASIA syndrome, breast implant illness. The paper reviews known facts about the disease, its characteristics, and statistical aspects.

Associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation.

The space radiation environment consists of multiple species of charged particles, including 28Si ions, that may impact brain function during and following missions. To develop biomarkers of the space radiation response, BALB/c and C3H female and male mice and their F2 hybrid progeny were irradiated with 28Si ions (350 MeV/n, 0.2 Gy) and tested for behavioral and cognitive performance 1, 6, and 12 months following irradiation. The plasma of the mice was collected for analysis of miRNA levels. Select pertinent brain regions were dissected for lipidomic analyses and analyses of levels of select biomarkers shown to be sensitive to effects of space radiation in previous studies. There were associations between lipids in select brain regions, plasma miRNA, and cognitive measures and behavioral following 28Si ion irradiation. Different but overlapping sets of miRNAs in plasma were found to be associated with cognitive measures and behavioral in sham and irradiated mice at the three time points. The radiation condition revealed pathways involved in neurodegenerative conditions and cancers. Levels of the dendritic marker MAP2 in the cortex were higher in irradiated than sham-irradiated mice at middle age, which might be part of a compensatory response. Relationships were also revealed with CD68 in miRNAs in an anatomical distinct fashion, suggesting that distinct miRNAs modulate neuroinflammation in different brain regions. The associations between lipids in selected brain regions, plasma miRNA, and behavioral and cognitive measures following 28Si ion irradiation could be used for the development of biomarker of the space radiation response.

The cadmium tolerance development of poplar callus is influenced by silicon.

Cadmium-tolerant plants were studied for their possible usage in phytoremediation techniques. However, their response to cadmium cations at a cellular level has not been properly studied. Silicon is a beneficial element that seems to change the plant's response to the Cd2+ presence. The aim of the present study was to investigate the Cd2+ tolerance patterns of poplar callus cells exposed to Cd+2 and/or Si over short and long cultivation periods. We determined the growth parameters of the callus, the growth dynamics, cell vitality, photosynthetic pigment concentrations and the activity of antioxidant enzymes. The effects were studied over short (21 days) and long (63 days) cultivation periods. The most important result proved that the poplar callus tissue is able to build up a tolerance to Cd2+ after a longer cultivation period. On the 63rd day of the cultivation, Cd2+ stressed calli showed improvement in studied parameters and the callus cells accumulated Cd2+ more efficiently than on the 21st day. Supplementation with Si in higher concentrations (2.5 mM and 5 mM) heightened the Cd-tolerance potential of the tissue. The treatment of Cd2+, and Si in a 2.5 mM concentration was the most efficient variant for Cd2+ removal from medium. The activity of antioxidant enzymes showed that poplar callus cells effectively develop tolerance against Cd2+ after a longer cultivation period.

Protons and High-Linear Energy Transfer Radiation Induce Genetically Similar Lymphomas With High Penetrance in a Mouse Model of the Aging Human Hematopoietic System.

PURPOSE: Humans are exposed to charged particles in different scenarios. The use of protons and high-linear energy transfer (LET) in cancer treatment is steadily growing. In outer space, astronauts will be exposed to a mixed radiation field composed of both protons and heavy ions, in particularly the long-term space missions outside of earth's magnetosphere. Thus, understanding the radiobiology and transforming potential of these types of ionizing radiation are of paramount importance. METHODS AND MATERIALS: We examined the effect of 10 or 100 cGy of whole-body doses of protons or 28Si ions on the hematopoietic system of a genetic model of aging based on recent studies that showed selective loss of the MLH1 protein in human hematopoietic stems with age. RESULTS: We found that Mlh1 deficient animals are highly prone to develop lymphomas when exposed to either low doses of protons or 28Si ions. The lymphomas that develop are genetically indistinguishable, in spite of different types of damage elicited by low- and high-LET radiation. RNA sequencing analyses reveal similar gene expression patterns, similar numbers of altered genes, similar numbers of single nucleotide variants and insertions and deletions, and similar activation of known leukemogenic loci. CONCLUSIONS: Although the incidence of malignancy is related to radiation quality, and increased due to loss of Mlh1, the phenotype of the tumors is independent of LET.

Comparison of silicon and metallic bifurcated stents in patients with malignant airway lesions.

INTRODUCTION AND OBJECTIVE: Silicon and metallic are two types of stents in use. In this study, we compared complications and long-term survival among patients who received silicon or fully covered, bifurcated self-expandable metallic stents (SEMS) for a malignant tracheobronchial obstruction and/or tracheo/bronchial oesophageal fistulas. METHODS: Patients in whom Y-shaped stents were used from January 2013 to June 2017 in our interventional pulmonology unit were evaluated retrospectively from patient files. RESULTS: Of the 47 patients, 30 (23 males, 76.7%) were in the silicon stent group and 17 (14 males, 82.4%) were in the covered SEMS group. No differences between the groups were detected in ECOG status, pathological properties of the disease, radiotherapy or chemotherapy history before the procedure, symptoms at presentation, or comorbidities. The most common symptom was dyspnoea (96.7% and 100%), and the most common comorbidity was chronic obstructive pulmonary disease (26.7% and 23.5%). A total of 20 complications (42.6%) were seen, with no significant difference between the groups (silicon, 40%; SEMS, 47.1%; P = . 62). Mean survival was 164.51 ± 38.83 days for the silicon stent group and 254.45 ± 103.32 days for the SEMS group (P = .588). No differences were observed in 30-, 90- or 180-day mortality between the two groups (P = .966, .846 and .534, respectively). CONCLUSIONS: No significant differences in symptom palliation, insertion safety, complication rate or survival were detected between the two types of stent.

Complications of silicone Y stents placed due to malignant airway stenosis.

INTRODUCTION: Malignant central airway obstruction around the main carina often requires placement of Y­shaped stents. In this study, we aimed to determine the safety of silicone Y stents placed around the main carina in the malignant airway obstruction by examining the long term complications, emergence times and treatment approaches of complications. MATERIALS AND METHODS: Between May 2012 and July 2015, 47 silicone Y stents were placed in 46 patients with malignant external compression or mixed type stenosis around the main carina. Patient stents were placed via rigid bronchoscopy under total intravenous anesthesia in operating room conditions. RESULT: In the half of the patients (23/46), stents were placed under urgent conditions due to acute respiratory failure. Stents were deployed successfully in all the patients. No procedure related deaths were observed. The median time of survival following stent insertion was 157 days. The total long-term complication rate of silicone Y stents was 28.3%. Mucostasis (8.7%) and migration (2.2%) were observed within the first month after placement of the silicone Y stents (median 18 days), stent-edge granulation tissue development (13.0%) was observed at the earliest one month (median 64, range 34-386 days) and stent-edge tumor tissue development (4.3%) were observed at the earliest 3 months (median 151, range 85-217 days). A total of 7 (15.2%) stents were removed, 2 of which were due to mucostasis and 5 of which were due to granulation tissue development. One patient's stent was replaced with a longer silicone Y stent due to stent-edge tumor tissue development. CONCLUSIONS: The best palliative treatment of malignant tumor stenosis around the main carina is still silicone Y stent placement, but the long-term complication rate can be high. For this group of patients, bronchoscopy to be performed at the first and third months after silicone Y stent placement may provide early detection of stent-edge tissue development.

Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste.

BACKGROUND: The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. MATERIALS AND METHODS: Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. RESULTS: No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. CONCLUSION: CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase.

Occupational exposure to photocopiers and their toners cause genotoxicity.

Photocopier machines are inevitable office equipment, but they are also sources of air pollution. Millions of people across the world are involved in the operation and maintenance of photocopiers. We aimed to evaluate the potential genotoxic effects of exposure to photocopiers in photocopier operators and maintenance personnel by Comet assay. This study involved 50 photocopier operators, 61 maintenance personnel and 52 controls. Both the photocopier exposed groups exhibited significantly increased DNA damage when compared to controls. Cumulative exposure to photocopiers was the most significant contributor for genotoxicity ( p < 0.001). Genotoxicity among photocopier maintenance personnel may be due to the presence of carbon black, iron, silicon, magnetite and the high levels of other elements in the photocopier toners. Genotoxicity among photocopier operators might be due to exposure to high levels of particulate matter and volatile organic compounds emitted by photocopiers during operation. Research is essential to improve toner manufacturing processes and chemical composition of toners to reduce genotoxicity. Clean technologies are the need of the day to cut down on particulate matter and volatile organic compound emissions from photocopiers.

Ultrapure laser-synthesized Si-based nanomaterials for biomedical applications: in vivo assessment of safety and biodistribution.

Si/SiOx nanoparticles (NPs) produced by laser ablation in deionized water or aqueous biocompatible solutions present a novel extremely promising object for biomedical applications, but the interaction of these NPs with biological systems has not yet been systematically examined. Here, we present the first comprehensive study of biodistribution, biodegradability and toxicity of laser-synthesized Si-SiOx nanoparticles using a small animal model. Despite a relatively high dose of Si-NPs (20 mg/kg) administered intravenously in mice, all controlled parameters (serum, enzymatic, histological etc.) were found to be within safe limits 3 h, 24 h, 48 h and 7 days after the administration. We also determined that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine without any toxicity effects. Finally, we found that intracellular accumulation of Si-NPs does not induce any oxidative stress damage. Our results evidence a huge potential in using these safe and biodegradable NPs in biomedical applications, in particular as vectors, contrast agents and sensitizers in cancer therapy and diagnostics (theranostics).

Silicon Injection Granulomata: 67Ga Citrate Findings in Free Silicon Buttock Augmentation.

Ga citrate is frequently used in the workup of fever of unknown origin. Here, we report a case of avid Ga-citrate in bilateral gluteal regions of a patient with a history of free silicon injection buttock augmentation referred for suspected diagnosis of sarcoidosis. CT findings were equivocal for inflammation/infection in the buttock region, and nuclear scintigraphy allowed for more definitive diagnosis.

Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC(1638N/+) Mice.

PURPOSE: There are uncertainties associated with the prediction of colorectal cancer (CRC) risk from highly energetic heavy ion (HZE) radiation. We undertook a comprehensive assessment of intestinal and colonic tumorigenesis induced after exposure to high linear energy transfer (high-LET) HZE radiation spanning a range of doses and LET in a CRC mouse model and compared the results with the effects of low-LET γ radiation. METHODS AND MATERIALS: Male and female APC(1638N/+) mice (n=20 mice per group) were whole-body exposed to sham-radiation, γ rays, (12)C, (28)Si, or (56)Fe radiation. For the >1 Gy HZE dose, we used γ-ray equitoxic doses calculated using relative biological effectiveness (RBE) determined previously. The mice were euthanized 150 days after irradiation, and intestinal and colon tumor frequency was scored. RESULTS: The highest number of tumors was observed after (28)Si, followed by (56)Fe and (12)C radiation, and tumorigenesis showed a male preponderance, especially after (28)Si. Analysis showed greater tumorigenesis per unit of radiation (per cGy) at lower doses, suggesting either radiation-induced elimination of target cells or tumorigenesis reaching a saturation point at higher doses. Calculation of RBE for intestinal and colon tumorigenesis showed the highest value with (28)Si, and lower doses showed greater RBE relative to higher doses. CONCLUSIONS: We have demonstrated that the RBE of heavy ion radiation-induced intestinal and colon tumorigenesis is related to ion energy, LET, gender, and peak RBE is observed at an LET of 69 keV/µm. Our study has implications for understanding risk to astronauts undertaking long duration space missions.

Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon ((28)Si) ions.

Although myeloid leukemia (ML) is one of the major health concerns from exposure to space radiation, the risk prediction for developing ML is unsatisfactory. To increase the reliability of predicting ML risk, a much improved understanding of space radiation-induced changes in the target cells, i.e. hematopoietic stem/progenitor cells (HSPCs), is important. We focused on the in vivo induction of late-occurring damage in HSPCs of mice exposed to (28)Si ions since such damage is associated with radiation-induced genomic instability (a key event of carcinogenesis). We gave adult male CBA/CaJ mice, known to be sensitive to radiation-induced ML, a whole-body exposure (2 fractionated exposures, 15 days apart, that totaled each selected dose, delivered at the dose-rate of 1 cGy/min) to various doses of 300 MeV/n (28)Si ions, i.e. 0 (sham controls), 0.1, 0.25, or 0.5 Gy. At 6 months post-irradiation, we collected bone marrow cells from each mouse (five mice per treatment-group) for obtaining the myeloid-lineage of HSPC-derived clones for analyses. We measured the frequencies of late-occurring chromosome aberrations (CAs), using the genome-wide multicolor fluorescence in situ hybridization method. The measurement of CAs was coupled with the characterization of the global DNA methylation patterns, i.e. 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC). A dose-dependent increase in the frequencies of CAs was detected (Analysis of Variance or ANOVA, p<0.01), indicating the induction of genomic instability after exposure of mice to 300 MeV/n (28)Si ions. Slight increases in the levels of 5 mC were observed in all treatment groups, as compared to the sham-control level. In contrast, there was a significant reduction in levels of 5 hmC (ANOVA, p<0.01). Since these endpoints were evaluated in the same mouse, our data suggested for the first time a link between a reduction in 5 hmC and genomic instability in HSPC-derived myeloid colonies of CBA/CaJ mice exposed to 300 MeV/n (28)Si ions.

Radiation-induced alterations in synaptic neurotransmission of dentate granule cells depend on the dose and species of charged particles.

The evaluation of potential health risks associated with neuronal exposure to space radiation is critical for future long duration space travel. The purpose of this study was to evaluate and compare the effects of low-dose proton and high-energy charged particle (HZE) radiation on electrophysiological parameters of the granule cells in the dentate gyrus (DG) of the hippocampus and its associated functional consequences. We examined excitatory and inhibitory neurotransmission in DG granule cells (DGCs) in dorsal hippocampal slices from male C57BL/6 mice at 3 months after whole body irradiation with accelerated proton, silicon or iron particles. Multielectrode arrays were used to investigate evoked field synaptic potentials, an extracellular measurement of synaptic excitability in the perforant path to DG synaptic pathway. Whole-cell patch clamp recordings were used to measure miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) in DGCs. Exposure to proton radiation increased synaptic excitability and produced dose-dependent decreases in amplitude and charge transfer of mIPSCs, without affecting the expression of γ-aminobutyric acid type A receptor α2, ß3 and γ2 subunits determined by Western blotting. Exposure to silicon radiation had no significant effects on synaptic excitability, mEPSCs or mIPSCs of DGCs. Exposure to iron radiation had no effect on synaptic excitability and mIPSCs, but significantly increased mEPSC frequency at 1 Gy, without changes in mEPSC kinetics, suggesting a presynaptic mechanism. Overall, the data suggest that proton and HZE exposure results in radiation dose- and species-dependent long-lasting alterations in synaptic neurotransmission, which could cause radiation-induced impairment of hippocampal-dependent cognitive functions.

Effects of 28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma.

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n 28Si or 600 MeV/n 56Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n 28Si ions, 600 MeV/n 56Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with 137Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that 28Si or 56Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, 28Si or 56Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the 28Si and 56Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.

[Physical methods to determine compatibility of implants].

The effect of the living organism on the polymer materials used for the manufacture of grids for implants. It is shown that the recipient's body is actively working to exogenous material , destroying its surface layer and forms around the implant insulating fibro-connective tissue capsule, the thickness of which depends on the severity of the organism's reaction to a foreign body. Proposed instrumental method of determining compatibility before surgery implant material with the recipient using an atomic force microscope (AFM).

Soybean Resistance to Cercospora sojina Infection Is Reduced by Silicon.

Frogeye leaf spot, caused by Cercospora sojina, is one of the most important leaf diseases of soybean worldwide. Silicon (Si) is known to increase the resistance of several plant species to pathogens. The cultivars Bossier and Conquista, which are susceptible and resistant, respectively, to frogeye leaf spot, supplied and nonsupplied with Si were examined for the activities of defense enzymes and the concentrations of total soluble phenolics (TSP) and lignin-thioglycolic acid (LTGA) derivatives at 8, 14, and 16 days after inoculation (dai) with C. sojina. The importance of cell wall degrading enzymes (CWDE) to the infection process of C. sojina and the effect of Si on their activities were also determined. Soybean plants were grown in hydroponic culture containing either 0 or 2 mM Si (-Si and +Si, respectively) and noninoculated or C. sojina inoculated. Severity of frogeye leaf spot was higher in cultivar Bossier plants than cultivar Conquista and also in the +Si plants compared with their -Si counterparts. Except for the concentrations of TSP and LTGA derivatives, activities of defense enzymes and the CWDE did not change for +Si noninoculated plants regardless of the cultivar. The activities of lipoxygenases, phenylalanine ammonia-lyases, chitinases, and polyphenoloxidases as well as the activities of CWDE decreased for the +Si inoculated plants. The results from this study demonstrated that defense enzyme activities decreased in soybean plants supplied with Si, which compromised resistance to C. sojina infection.

Dust exposure is associated with increased lung function loss among workers in the Norwegian silicon carbide industry.

OBJECTIVES: To investigate the relationship between dust exposure and annual change in lung function among employees in Norwegian silicon carbide (SiC) plants using a quantitative job exposure matrix (JEM) regarding total dust. METHODS: All employees, 20-55 years of age by inclusion (n=456), were examined annually for up to 5 years (1499 examinations). Spirometry was performed at each examination, and a questionnaire encompassing questions of respiratory symptoms, smoking status, job and smoking history, and present job held was completed. A JEM was constructed based on 1970 personal total dust exposure measurements collected during the study period. The association between lung function and total dust exposure was investigated using linear mixed models. RESULTS: The annual change in forced expiratory volume (FEV) in one second per squared height, FEV1/height(2), per mg/m(3) increase in dust exposure was -2.3 (95% CI -3.8 to -0.79) (mL/m(2))×year(-1). In an employee of average height (1.79 m) and exposure (1.4 mg/m(3)) the estimated contribution to the annual change in FEV1 associated with dust was 10.4 mL/year. The annual change in FEV1/height(2) in current, compared with non-smokers was -1.9 (-7.2 to 3.4) (mL/m(2))×year(-1). The estimated overall annual decline in FEV1 among current and non-smokers in the highest exposed group was -91.2 (-124.3 to -58.1) (mL/m(2))×year(-1) and -49.0 (-80.2 to -17.8) (mL/m(2))×year(-1), respectively. CONCLUSIONS: Dust exposure, expressed by a quantitative JEM, was found to be associated with an increased yearly decline in FEV1 in employees of Norwegian SiC plants.

Persistence of apoptosis and inflammatory responses in the heart and bone marrow of mice following whole-body exposure to ²8Silicon (²8Si) ions.

It has been well established that the bone marrow (BM) is a radiosensitive tissue, but the radiosensitivity of the heart is poorly understood. In this study, we investigated the comparative effects of ²8Silicon (²8Si) ions (one type of heavy ion found in space) on tissue from the heart and the BM of exposed mice. We gave adult male CBA/CaJ mice a whole-body exposure to a total dose of 0, 0.1, 0.25, or 0.5 Gy of 300 MeV/nucleon (n) ²8Si ions, using a fractionated schedule (two exposures, 15 days apart that totaled each selected dose). The heart and BM were collected from 5 mice per treatment group at various times up to 6 months post-irradiation. In each mouse, we obtained tissue lysates from the heart and from the total population of BM cells for measuring the levels of cleaved poly (ADP-ribose) polymerase (cleaved PARP, a marker of apoptotic cell death) and the levels of activated nuclear factor-kappa B (NF-κB) and selected NF-κB-regulated cytokines known to be involved in inflammatory responses. Our data showed that, up to 6 months post-irradiation, the levels of apoptotic cell death and inflammatory responses in tissues from the heart and BM collected from exposed mice were statistically higher than those in sham controls. Hence, these findings are suggestive of chronic apoptotic cell death and inflammation in both tissues after exposure to ²8Si ions. In summary, our data are indicative of a possible association between exposure to ²8Si ions during space flight and long-term health risk.

Lung cancer incidence among Norwegian silicon carbide industry workers: associations with particulate exposure factors.

OBJECTIVES: An increased lung cancer risk associated with total dust exposure in the silicon carbide (SiC) industry has previously been reported. The aim of the present study was to examine the relative importance of specific exposure factors by using a comprehensive, historic job exposure matrix based on about 8000 measurements. METHODS: Cumulative exposure to total and respirable dust, respirable quartz, cristobalite, and SiC particles and SiC fibres was assessed for 1687 long-term workers employed during 1913-2003 in the Norwegian SiC industry. Standardised incidence ratios for lung cancer, with follow-up during 1953-2008, were calculated stratified by cumulative exposure categories. Poisson regression analyses were performed using both categorised and log-transformed cumulative exposure variables. RESULTS: The lung cancer incidence was about twofold increased at the highest level of exposure to each of the exposure factors (standardised incidence ratios 1.9-2.3 for all agents). Internal analyses showed associations between exposure level and lung cancer incidence for all investigated factors, but a significant trend only for total dust and cristobalite. In multivariate analyses, cristobalite showed the most consistent associations, followed by SiC fibres. CONCLUSIONS: The results indicated that crystalline silica in the form of cristobalite was the most important occupational exposure factor responsible for lung cancer excess in the Norwegian SiC industry. SiC fibres seemed to have an additional effect.