Genotoxic responses to titanium dioxide nanoparticles and fullerene in gpt delta transgenic MEF cells

Background  

Titanium dioxide (TiO₂) nanoparticles and fullerene (C₆₀) are two attractive manufactured nanoparticles with great promise in industrial and medical applications. However, little is known about the genotoxic response of TiO₂ nanoparticles and C₆₀ in mammalian cells. In the present study, we determined the mutation fractions induced by either TiO₂ nanoparticles or C₆₀ in gpt delta transgenic mouse primary embryo fibroblasts (MEF) and identified peroxynitrite anions (ONOO^-) as an essential mediator involved in such process.     

Asbestos, carbon nanotubes and the pleural mesothelium: a review of the hypothesis regarding the role of long fibre retention in the parietal pleura, inflammation and mesothelioma

Background

Increasing environmental and occupational exposures to nanoparticles (NPs) warrant deeper insight into the toxicological mechanisms induced by these materials. The present study was designed to characterize the cell death induced by carbon black (CB) and titanium dioxide (TiO₂) NPs in bronchial epithelial cells (16HBE14o- cell line and primary cells) and to investigate the implicated molecular pathways.

Results

Detailed time course studies revealed that both CB (13 nm) and TiO₂(15 nm) NP exposed cells exhibit typical morphological (decreased cell size, membrane blebbing, peripheral chromatin condensation, apoptotic body formation) and biochemical (caspase activation and DNA fragmentation) features of apoptotic cell death. A decrease in mitochondrial membrane potential, activation of Bax and release of cytochrome c from mitochondria were only observed in case of CB NPs whereas lipid peroxidation, lysosomal membrane destabilization and cathepsin B release were observed during the apoptotic process induced by TiO₂ NPs. Furthermore, ROS production was observed after exposure to CB and TiO₂ but hydrogen peroxide (H₂O₂) production was only involved in apoptosis induction by CB NPs.

Conclusions

Both CB and TiO₂ NPs induce apoptotic cell death in bronchial epithelial cells. CB NPs induce apoptosis by a ROS dependent mitochondrial pathway whereas TiO₂ NPs induce cell death through lysosomal membrane destabilization and lipid peroxidation. Although the final outcome is similar (apoptosis), the molecular pathways activated by NPs differ depending upon the chemical nature of the NPs.     

Cobalt nanoparticles induce lung injury,DNA damage and mutations in mice

Background

We and other groups have demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused oxidative stress and inflammation, which have been shown to be strongly associated with genotoxic and carcinogenic effects. However, few studies have reported Nano-Co-induced genotoxic effects in vivo. Here, we propose that Nano-Co may have high genotoxic effects due to their small size and high surface area, which have high capacity for causing oxidative stress and inflammation.

Methods

gpt delta transgenic mice were used as our in vivo study model. They were intratracheally instilled with 50 μg per mouse of Nano-Co. At day 1, 3, 7 and 28 after exposure, bronchoalveolar lavage (BAL) was performed and the number of neutrophils, CXCL1/KC level, LDH activity and concentration of total protein in the BAL fluid (BALF) were determined. Mouse lung tissues were collected for H&E staining, and Ki-67, PCNA and γ-H2AX immunohistochemical staining. 8-OHdG level in the genomic DNA of mouse lungs was determined by an OxiSelect? Oxidative DNA Damage ELISA Kit, and mutant frequency and mutation spectrum in the gpt gene were also determined in mouse lungs at four months after Nano-Co exposure by 6-TG selection, colony PCR, and DNA sequencing.

Results

Exposure of mice to Nano-Co (50 μg per mouse) resulted in extensive acute lung inflammation and lung injury which were reflected by increased number of neutrophils, CXCL1/KC level, LDH activity and concentration of total protein in the BALF, and infiltration of large amount of neutrophils and macrophages in the alveolar space and interstitial tissues. Increased immunostaining of cell proliferation markers, Ki-67 and PCNA, and the DNA damage marker, γ-H2AX, was also observed in bronchiolar epithelial cells and hyperplastic type II pneumocytes in mouse lungs at day 7 after Nano-Co exposure. At four months after exposure, extensive interstitial fibrosis and proliferation of interstitial cells with inflammatory cells infiltrating the alveolar septa were observed. Moreover, Nano-Co caused increased level of 8-OHdG in genomic DNA of mouse lung tissues. Nano-Co also induced a much higher mutant frequency as compared to controls, and the most common mutation was G:C to T:A transversion, which may be explained by Nano-Co-induced increased formation of 8-OHdG.

Conclusion

Our study demonstrated that exposure to Nano-Co caused oxidative stress, lung inflammation and injury, and cell proliferation, which further resulted in DNA damage and DNA mutation. These findings have important implications for understanding the potential health effects of nanoparticle exposure.

     

Preparation of a Novel Class of Cationic Gemini Imidazolium Surfactants Containing Amide Groups as the Spacer: Their Surface Properties and Antimicrobial Activity

A class of novel cationic Gemini imidazolium surfactants containing amide groups as the spacer were synthesized from ethylenediamine and 1-bromoalkane(C₈, C₁₀, C₁₂, C₁₄, C₁₆) by N-alkylation to get N,N′-dialkyl ethylenediamine (1a–e), 1a–e was further reacted with chloroacetyl chloride by N-acylation to get N,N′-(ethane-1,2-diyl)bis(2-chloro-N-alkylacetamide) (2a–e), which was further reacted respectively with 1-methyl imidazole by quaternized to form the surfactant molecule, N,N′-((ethane-1,2-diyl)bis(alkyl-azanediyl)bis(2-oxoethane-2,1-diyl)) bis(1-methyl-1H-imidazol-3-ium) dichloride. The structures of intermediates (1a–e) and (2a–e) were characterized by IR and ¹H NMR. The structures of the surfactants (3a–e) were characterized by IR, ¹H-NMR and ¹³C-NMR and element analysis. The critical micelle concentrations (CMC) of 3a–e were determined by the conductivity method at 25 °C. The CMC values decreased with increasing the length of the hydrophobic chain. The surfactants (3a–e) showed good foaming stability, emulsion ability and wetting ability. The surfactants (3a–e) also have good antimicrobial activity against Staphylococcus aureus, Escherichia coli and Bacillus subtilis.     

Study on Isothermal Formation Dynamics of Calcium Barium Sulphoaluminate Mineral

The formation dynamics of calcium barium sulphoaluminate mineral with the composition of 2.75CaO·1.25BaO·3Al₂O₃·SO₃ (C_2.75B_1.25A₃ $\overline{\text{S}}$ S ¯ ) was studied. The results suggest that, under the preparative conditions, the formation of C_2.75B_1.25A₃ $\overline{\text{S}}$ S ¯ mineral is controlled by a diffusion mechanism from 1,100 to 1,380 °C; and, the formation dynamics fits nicely with D ₄ = 1 ? 2α/3 ? (1 ? α)^2/3 = Kt. From 1,100 to 1,300 °C, the apparent activation energy is 227.45 kJ mol^?1. From 1,300 to 1,380 °C, the apparent activation energy decreases to 175.94 kJ mol^?1, making the formation of C_2.75B_1.25A₃ $\overline{\text{S}}$ S ¯ mineral faster and easier.     

Recovery from a cycling time trial is enhanced with carbohydrate-protein supplementation vs. isoenergetic carbohydrate supplementation

Background

In this study we assessed whether a liquid carbohydrate-protein (C+P) supplement (0.8 g/kg C; 0.4 g/kg P) ingested early during recovery from a cycling time trial could enhance a subsequent 60 min effort on the same day vs. an isoenergetic liquid carbohydrate (CHO) supplement (1.2 g/kg).

Methods

Two hours after a standardized breakfast, 15 trained male cyclists completed a time trial in which they cycled as far as they could in 60 min (AM_ex) using a Computrainer indoor trainer. Following AM_ex, subjects ingested either C+P, or CHO at 10, 60 and 120 min, followed by a standardized meal at 4 h post exercise. At 6 h post AM_ex subjects repeated the time trial (PM_ex).

Results

There was a significant reduction in performance for both groups in PM_ex versus AM_ex. However, performance and power decreases between PM_ex and AM_ex were significantly greater (p ≤ 0.05) with CHO (-1.05 ± 0.44 km and -16.50 ± 6.74 W) vs C+P (-0.30 ± 0.50 km and -3.86 ± 6.47 W). Fat oxidation estimated from RER values was significantly greater (p ≤ 0.05) in the C+P vs CHO during the PM_ex, despite a higher average workload in the C+P group.

Conclusion

Under these experimental conditions, liquid C+P ingestion immediately after exercise increases fat oxidation, increases recovery, and improves subsequent same day, 60 min efforts relative to isoenergetic CHO ingestion.     

Carbon black nanoparticle instillation induces sustained inflammation and genotoxicity in mouse lung and liver

Background

Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo.

Methods

We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR.

Results

Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver.

Conclusions

Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.     

A living cell quartz crystal microbalance biosensor for continuous monitoring of cytotoxic responses of macrophages to single-walled carbon nanotubes

Background

There is growing evidence that exposure to small size particulate matter increases the risk of developing cardiovascular disease.

Methods

We investigated plaque progression and vasodilatory function in apolipoprotein E knockout (ApoE ^-/-) mice exposed to TiO₂. ApoE ^-/- mice were intratracheally instilled (0.5 mg/kg bodyweight) with rutile fine TiO₂ (fTiO₂, 288 nm), photocatalytic 92/8 anatase/rutile TiO₂ (pTiO₂, 12 nm), or rutile nano TiO₂ (nTiO₂, 21.6 nm) at 26 and 2 hours before measurement of vasodilatory function in aorta segments mounted in myographs. The progression of atherosclerotic plaques in aorta was assessed in mice exposed to nanosized TiO₂ (0.5 mg/kg bodyweight) once a week for 4 weeks. We measured mRNA levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue to assess pulmonary inflammation and vascular function. TiO₂-induced alterations in nitric oxide (NO) production were assessed in human umbilical vein endothelial cells (HUVECs).

Results

The exposure to nTiO₂ was associated with a modest increase in plaque progression in aorta, whereas there were unaltered vasodilatory function and expression levels of Mcp-1, Mip-2, Vcam-1, Icam-1 and Vegf in lung tissue. The ApoE ^-/- mice exposed to fine and photocatalytic TiO₂ had unaltered vasodilatory function and lung tissue inflammatory gene expression. The unaltered NO-dependent vasodilatory function was supported by observations in HUVECs where the NO production was only increased by exposure to nTiO₂.

Conclusion

Repeated exposure to nanosized TiO₂ particles was associated with modest plaque progression in ApoE ^-/- mice. There were no associations between the pulmonary TiO₂ exposure and inflammation or vasodilatory dysfunction.     

Full Characterisation of Crambe abyssinica Hochst. Seed Oil

This work was dedicated to reporting the full chemical and physical characterisation of Crambe abyssinica Hochst. seed oil. The oil from the seeds was extracted using n-hexane. The seeds contain about 30?% oil. Density, refractive index, colour, smoke point, viscosity, acidity, saponification value, iodine value, fatty acid methyl esters, the relative position of fatty acids in C₁ and C₃ carbon glycerol, sterols, tocopherols, peroxide value, $ \mathop E\nolimits_{{1{\text{cm}}}}^{1\,\% } $ at 232?nm, and the susceptibility to oxidation measured by the Rancimat method were determined. The oil was found to contain high levels of unsaturated fatty acids, especially C22:1 (63.77?%). The dominant saturated acid was C22:0 (2.14?%). The oil was also found to contain high levels of β-sitosterol (51.93?%), campestanol (21.98?%), and brassicasterol (12.35?%). α-, γ-, and δ-Tocopherols were detected up to levels of 7.67, 125.04, and 3.99?mg/kg, respectively. The induction period (at 110?°C and 20?l/h) of the oil was 8.83?h. The relative position of fatty acids in C₁ and C₃ position was as follows: linoleic 0.45?%, oleic 8.84?%, and erucic 90.72?%. The thermal profile of the oil presented a single peak at ?20.94?°C.     

Esterification of acrylic acid with ethanol using pervaporation membrane reactor

Esterification of acrylic acid with ethanol was carried out using an in-situ reactor with an integrated pervaporation assembly (IPAE) made of polyvinyl alcohol (PVA) membrane and was compared with a non-integrated (NIE) system. Effect of reaction temperature (T _r ), catalyst loading (C _C ), molar ratios of reactants (MR) and ratio of effective membrane area to unit volume of reaction mixture (S/V _o ) on kinetics of esterification reaction were studied. Conversions achieved in IPAE were found to be distinctly higher than the NIE. The highest conversion of acrylic acid was obtained as 83.3% at T _r =60 °C, M _R =3 : 1, C _C =2% and S/V _o =14.1 m^?1. Equilibrium conversion of acrylic acid in NIE was obtained as 55.1% at 60 °C, 1 : 1 in 7 h, while using IPAE conversion enhances to 67.6%. Esterification of acrylic acid and ethanol with presently studied operating parameters provides a new approach to existing literature reported esterification-pervaporation system.     

Synthesis and characterization of novel polyhydrazides containing pendant amide-imide-pyridine moiety

Eight novel polyhydrazides (PH _a4?Ch3 ) were prepared from the reaction of two novel diacids, 5-(2-(6-methyl pyridine-2-yl)-1,3-dioxo isoindoline-6-carboxamido) isophthalic acid (3) and 5-(2-(4-methyl pyridine-2-yl)-1,3-dioxo isoindoline-6-carboxamido) isophthalic acid (4), with four dihydrazides by interfacial polycondensation. These polymers have moderate inherent viscosities (0.12?C0.17?dL/g) and are readily soluble in polar aprotic solvents. They start to decompose (T _10%) above 187?°C and display glass transition temperatures in the range of 130.3?C156.3?°C. All polymers could be thermally converted into the corresponding polyoxadiazole approximately in the region of 250?°C, as evidenced by the DSC thermograms. All of the above polymers were fully characterized by FT-IR and ¹HNMR spectroscopy, TGA, DSC, and inherent viscosity measurement.     

Structure and electrical properties of heat-treated fullerene nanowhiskers as potential energy device materials

Fine carbon tubes “fullerene shell tubes (FSTs)” have been found among the C₆₀ nanowhiskers heat-treated under vacuum at a temperature higher than 600 °C. FSTs with open ends have been found as well as FSTs with closed spherical ends. It has been also found that the FSTs can be easily prepared by the heat treatment of the C₆₀ whiskers prepared by using C₆₀ powders containing (η²-C₆₀)Pt(PPh₃)₂. Since the high temperature-treated fullerene (nano)whiskers exhibit a high specific surface area and a good electrical conductivity, they are expected to be utilized as new electrode materials for fuel cells.     

Ionic Liquid-Supported Bis-(salicylaldimine) Nickel Complexes: Robust and Recyclable Catalysts for Ethylene Oligomerization in Biphasic Solvent System

Two new ionic liquid-supported bis-(salicylaldimine) Ni(II) complexes Ni[2-(O)C₆H₄CH=N(CH₂)₃(methylimidazole)Br]₂ (1) and Ni[3, 5-^tBu₂-2-(O)C₆H₂CH=N(CH₂)₃(methylimidazole)Br]₂ (2) have been synthesized and characterized. Ethylene oligomerizations were carried out with these two complexes in biphasic solvent systems consisting of chloroaluminate ionic liquid and n-heptane or toluene under mild reaction conditions. In the presence of diethylaluminum chloride, both complexes 1 and 2 are highly active for ethylene oligomerization. The olefinic products can be easily separated from the catalytic ionic liquid phase by simple decantation, and the nickel catalysts can be reused in successive ethylene oligomerization cycles. GC-MS analyzes showed that the obtained oligomers contained mainly C4, C6, and C8 olefins.     

Synthesis and Structural Characterization of Triorganotin(IV) Derivatives with 2,2′-Thiodiglycolic Acid and 3,3′-Thiodipropionic Acid

The synthesis and structural characterization of four novel triorganotin(IV) complexes, {(R₃Sn)₂[C₂H₄S(COO)₂]} _n (R = Me: 1), {(R₃Sn)₄[C₂H₄S(COO)₂]₂} _n (R = nBu: 2), {(R₃Sn)₂[C₄H₈S(COO)₂]} _n (R = Me: 3; nBu: 4) were obtained by the reaction of 2,2′-thiodiglycolic acid, 3,3′-thiodipropionic acid and the corresponding R₃SnCl (R = Me, nBu) with potassium hydroxide in methanol. All the complexes were characterized by elemental analysis, Fourier transform infrared and nuclear magnetic resonance (¹H, ¹³C, ¹¹⁹Sn) spectroscopies, X-ray crystallography and thermogravimetric analyses. The crystal structures show that 1 has 2D network structure in which 2,2′-thiodiglycolic acid acts as a tetradentate ligand coordinating to the trimethyltin(IV) ions. Complexes 2, 3, and 4 are 3D metal-organic framework structures in which the deprotoned acids act as a tetradentate ligand afforded by four oxygen atoms.     

Solution-Combustion Synthesis of LiNi<Subscript>1/3</Subscript>Co<Subscript>1/3</Subscript>Mn<Subscript>1/3</Subscript>O<Subscript>2</Subscript> as a Cathode Material for Lithium-Ion Batteries

A cathode material for lithium-ion batteries–LiNi_1/3Co_1/3Mn_1/3O₂–was prepared by solution combustion synthesis and characterized by XRD, SEM, and galvanostatic charge/discharge cycling. The sample calcined at 950°C for 10 h showed best charge/discharge performance. An initial discharge capacity (C) of 150.5 mA h g^–1 retained 95.7% of its value after 75 charge/discharge cycles at I_c = 14 mA g^–1 (0.2C rate), I_d = 70 mA g^–1 (0.5C rate).     

Optimized dispersion of nanoparticles for biological in vitro and in vivo studies

Background

The aim of this study was to establish and validate a practical method to disperse nanoparticles in physiological solutions for biological in vitro and in vivo studies.

Results

TiO₂ (rutile) dispersions were prepared in distilled water, PBS, or RPMI 1640 cell culture medium. Different ultrasound energies, various dispersion stabilizers (human, bovine, and mouse serum albumin, Tween 80, and mouse serum), various concentrations of stabilizers, and different sequences of preparation steps were applied. The size distribution of dispersed nanoparticles was analyzed by dynamic light scattering and zeta potential was measured using phase analysis light scattering. Nanoparticle size was also verified by transmission electron microscopy. A specific ultrasound energy of 4.2 × 10⁵ kJ/m³ was sufficient to disaggregate TiO₂ (rutile) nanoparticles, whereas higher energy input did not further improve size reduction. The optimal sequence was first to sonicate the nanoparticles in water, then to add dispersion stabilizers, and finally to add buffered salt solution to the dispersion. The formation of coarse TiO₂ (rutile) agglomerates in PBS or RPMI was prevented by addition of 1.5 mg/ml of human, bovine or mouse serum albumin, or mouse serum. The required concentration of albumin to stabilize the nanoparticle dispersion depended on the concentration of the nanoparticles in the dispersion. TiO₂ (rutile) particle dispersions at a concentration lower than 0.2 mg/ml could be stabilized by the addition of 1.5 mg/ml albumin. TiO₂ (rutile) particle dispersions prepared by this method were stable for up to at least 1 week. This method was suitable for preparing dispersions without coarse agglomerates (average diameter < 290 nm) from nanosized TiO₂ (rutile), ZnO, Ag, SiO_x, SWNT, MWNT, and diesel SRM2975 particulate matter.

Conclusion

The optimized dispersion method presented here appears to be effective and practicable for preparing dispersions of nanoparticles in physiological solutions without creating coarse agglomerates.     

Heating and cooling of flocculated and non-flocculated slurries in tubular heat exchangers

The distinctly different turbulent heat transfer characteristics of flocculated kaolin slurries are compared with nonflocculated coal slurries via modified J-factor correlation forms for tubular exchangers. Both slurry types were statistically best-fitted with the approximate solution Bingham plastic flow model in preference to the local shear power law. In addition, the first known turbulent slurry heat transfer cooling results are presented along with the heating results. No distinction was made between heating and cooling correlation forms because of a random scatter of experimental points. Experimental results were interpreted as follows A. Flocculated kaolin slurries J_H = (h/C_pG) (C/K₁)^2;3= 0.027(DVρ/μLe^B?)^0.2 11%ω < %ω Solids < 24%ω Maximum Deviations: + 19.3%, ? 17.8% B. Non-flocculated coal slurries J_w = (h/C_pG)(C_pμLe^B?/k_w)^2/3e^?B?/4) =0.0285 (DVρ/ μLe^B?)^?0.2 13%_w > %w Solids < 33.5%. Maximum Deviations: + 17.8%, - 11.1%     

Deposition of C60, C70 and C84 fullerene molecules, in benzene via a change of the fluid state, from a gas–liquid two phase region to the critical point

We dissolve C₆₀, C₇₀ or C₈₄ molecules in benzene and change the fluid state from a gas–liquid two-phase region (25.0 °C) to the critical point (289.0 °C) and from the critical point to the original state (25.0 °C) along the gas–liquid coexistence curve. We find that particle-like and whisker-like nano/micro clusters, which are composed of C₆₀ molecules, deposit on the surface of a silicon substrate placed vertically in C₆₀/benzene solution during the temperature change, whereas no appreciable clusters are detected on the silicon substrate in either C₇₀/benzene or C₈₄/benzene solutions. The clusters, in which fcc lattice structures are formed by C₆₀ molecules, remain stable in the solution. The present result suggests that C₆₀ molecules can be separated and extracted from a mixture of C₆₀, C₇₀ and C₈₄ molecules dissolved in benzene.     

3D Pillar-Layered Zn(II) Compound with 6-Connected pcu Topology: Synthesis,Structure and Luminescent Properties for Sensing of Nitrobenzene

A new Zn(II) compound, namely {[Zn(atz)(C₂O₄)_0.5]·H₂O}_n (1 Hatz = 3-amino-1,2,4-triazole), has been synthesized by the hydrothermal reactions of Zn(NO₃)₂, Hatz and H₂C₂O₄. Single crystal X-ray structure analysis reveals that compound 1 features a 3D porous pillar-layer structure with 6-connected pcu topology. The free water molecules are filled in the 1D channels. Thermal analysis reveals that it can be stable up to 347 °C. Luminescence investigation for 1 reveals that it can be used as a good candidate for sensing of nitrobenzene.