Rationale: Phosphate (Pi) is an essential nutrient to living organisms. Recent surveys indicate that the intake of Pi has increased steadily. Our previous studies have indicated that elevated Pi activates the Akt signaling pathway. An increased knowledge of the response of lung cancer tissue to high dietary Pi may provide an important link between diet and lung tumorigenesis. Objectives: The current study was performed to elucidate the potential effects of high dietary Pi on lung cancer development. Methods: Experiments were performed on 5-week-old male K-ras LA1 lung cancer model mice and 6-week-old male urethane-induced lung cancer model mice. Mice were fed a diet containing 0.5% Pi (normal Pi) and 1.0% Pi (high Pi) for 4 weeks. At the end of the experiment, all mice were killed. Lung cancer development was evaluated by diverse methods. Measurement and Main Results: A diet high in Pi increased lung tumor progression and growth compared with normal diet. High dietary Pi increased the sodium-dependent inorganic phosphate transporter2b protein levels in the lungs. High dietary consumption of Pi stimulated pulmonary Akt activity while suppressing the protein levels of tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 as well as Akt binding partner carboxyl-terminal modulator protein, resulting in facilitated cap-dependent protein translation. In addition, high dietary Pi significantly stimulated cell proliferation in the lungs of K-ras LA1 mice. Conclusions: Our results showed that high dietary Pi promoted tumorigenesis and altered Akt signaling, thus suggesting that careful regulation of dietary Pi may be critical for lung cancer prevention as well as treatment.
Inhaled Fluorescent Magnetic N a n o p a r t i c l e s I n d u c e d E x t r a m e d u l l a r yHematopoiesis in the Spleen of Mice: Jung-Taek KWON, et al. Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Korea-Objectives: Nanomaterials are used in a wide variety of industrial materials such as semiconductors, magnetic resonance imaging, gene delivery carriers for gene therapy and many others; thus, human seems to be frequently exposed to them. Such diverse applications of nanoparticles elicit the need to identify the positive aspects of nanomaterials while avoiding the potential toxic effects. In this study, inhalation toxicity of manufactured nanomaterials using fluorescent magnetic nanoparticles (FMNPs) was assessed to address the issue of potential nanoparticle toxicity. Methods: Biological samples from a previous mouse FMNP exposure experiment were analyzed for potential FMNP toxicity. Mice inhaled FMNPs for 4 wk through a nose-only exposure chamber developed by our group for 4 wk and the potential toxicity of FMNPs was analyzed. Results: The nanoparticle distribution by scanning mobility particle sizer (SMPS) analysis showed that the mean values of number concentration (mass concentrations) in the nose-only exposure c h a m b e r w e r e m a i n t a i n e d a t 4 . 8 9 ×1 0 5 / c m 3 (approximately 159.4 µg/m 3 ) for the low concentration and 9.34×10 5 /cm 3 (approximately 319.5 µg/m 3 ) for the high concentration, respectively. Inhalation of FMNPs caused a decrease of body weight and significant changes of white blood cells (WBCs) levels in whole blood. The FMNPs induced extramedullary hematopoiesis in the spleen without having a pulmonary effect. Conclusions: Our results support the proposition that extensive toxicity evaluation is needed for practical applications of anthropogenic nanomaterials and suggest that careful regulation of nanoparticle applications may be necessary to maintain a high quality of life as well as for facilitating the development of nanotechnology. (J Occup Health 2009; 51: 423-431)
In the workplace, the arsenic is used in the semiconductor production and the manufacturing of pigments, glass, pesticides and fungicides. Therefore, workers may be exposed to airborne arsenic during its use in manufacturing. The purpose of this study was to evaluate the potential toxicity of particulate matters (PMs) doped with arsenic (PMs-Arsenic) using a rodent model and to compare the genotoxicity in various concentrations and to examine the role of PMs-Arsenic in the induction of signaling pathway in the lung. Mice were exposed to PMs 124.4 ± 24.5 μg/m3 (low concentration) , 220.2 ± 34.5 μg/m3 (middle concentration) , 426.4 ± 40.3 μg/m3 (high concentration) doped with arsenic 1.4 μg/m3 (Low concentration) ,2.5 μg/m3 (middle concentration) , 5.7 μg/m3 (high concentration) for 4 wks (6 h/d, 5 d/wk) , respectively in the whole-body inhalation exposure chambers. To determine the level of genotoxicity, Chromosomal aberration (CA) assay in splenic lymphocytes and Supravital micronucleus (SMN) assay were performed. Then, signal pathway in the lung was analyzed. In the genotoxicity experiments, the increases of aberrant cells were concentration-dependent. Also, PMs-arsenic caused peripheral blood micronucleus frequency at high concentration. The inhalation of PMs-Arsenic increased an expression of phosphorylated Akt (p-Akt: protein kinase B) and phpsphorylated mammalian target of rapamycin (p-mTOR) at high concentration group. Taken together, inhaled PMs-Arsenic caused genotoxicity and altered Akt signaling pathway in the lung. Therefore, the inhalation of PMs-Arsenic needs for a careful risk assessment in the workplace.
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