Fathi Moussa

In vivo behavior of large doses of ultrashort and full-length single-walled carbon nanotubes after oral and intraperitoneal administration to Swiss mice.

Carbon nanotube (CNT) materials are of special interest as potential tools for biomedical applications. However, available toxicological data concerning single-walled carbon nanotubes (SWNTs) and multiwalled carbon nanotubes (MWNTs) remain contradictory. Here, we compared the effects of SWNTs as a function of dose, length, and surface chemistry in Swiss mice. Transmission electron microscopy (TEM), Raman, near-infrared (NIR), and X-ray photoelectron spectroscopies have been used to characterize the tested materials. The dose of SWNT materials used in this study is considerably higher than that proposed for most biomedical applications, but it was deemed necessary to administer such large doses to accurately assess the toxicological impact of the materials. In an acute toxicity test, SWNTs were administered orally at a dose level of 1000 mg/kg bodyweight (b.w.). Neither death nor growth or behavioral troubles were observed. After intraperitoneal administration, SWNTs, irrespective of their length or dose (50-1000 mg/kg b.w.), can coalesce inside the body to form fiberlike structures. When structure lengths exceeded 10 mum, they irremediably induced granuloma formation. Smaller aggregates did not induce granuloma formation, but they persisted inside cells for up to 5 months after administration. Short (<300 nm) well-individualized SWNTs can escape the reticuloendothelial system to be excreted through the kidneys and bile ducts. These findings suggest that if the potential of SWNTs for medical applications is to be realized, they should be engineered into discrete, individual molecule-like species.

Toxicity studies of fullerenes and derivatives.

Due to their unique properties, fullerenes, a model of carbon-based nanoparticles, have attracted considerable interest in many fields of research including material science and biomedical applications. The potential and the growing use of fullerenes and their mass production have raised several questions about their safety and environmental impact. Available data clearly shows that pristine C60 has no acute or sub-acute toxicity in a large variety of living organisms, from bacteria and fungal to human leukocytes, and also in drosophila, mice, rats and guinea pigs. In contrast to chemically--either covalently or noncovalently--modified fullerenes, some C60 derivatives can be highly toxic. Furthermore, under light exposure, C60 is an efficient singlet oxygen sensitizer. Therefore, if pristine C60 is absolutely nontoxic under dark conditions, this is not the case under UV-Visible irradiation and in the presence of O2 where ffullerene solutions can be highly toxic through 1O2 formation. This chapter offers a general review of the studies on the toxicity of [60]fullerene or C60, the most abundant fullerene, and its derivatives.

Cytotoxicity and photocytotoxicity of a dendritic C60 mono-adduct and a malonic acid C60 tris-adduct on Jurkat cells

The cytotoxic and photocytotoxic effects of two water-soluble fullerene derivatives, a dendritic C(60) mono-adduct and the malonic acid C(60) tris-adduct were tested on Jurkat cells. Cell growth and vitality were determined by a cell counting and staining technique. After 2 weeks cultivation in the presence of the fullerene derivatives, it was found that only the dendritic mono-adduct inhibits cell growth (within 2 weeks the cell number decreased to 19%), whereas the tris-malonic acid adduct has little effect. The growth inhibition is reversible; cultivating the same cells further in the absence of fullerene, the cell number increased to 106.4%. Other experiments showed that these fullerene derivatives become toxic when irradiated with UVA or UVB light. The cell death is mainly caused by membrane damage and it is UV dose-dependent. Tris-malonic acid fullerene was found to be more phototoxic than the dendritic derivative. This result is in contrast to the singlet oxygen quantum yields determined for the two compounds. We propose that the two fullerene derivatives may interact with the cell membrane in different ways thus causing the observed effects. Further experiments will be done to determine the location and concentration of the two compounds in and on the cells.

Quantitative analysis of C60 fullerene in blood and tissues by high-performance liquid chromatography with photodiode-array and mass spectrometric detection

A high-performance liquid chromatographic (HPLC) assay method for C60 fullerene, in blood, liver and spleen using photodiode-array detection or mass spectrometric detection (LC-MS) and C70 fullerene, as the internal standard, is described. The recovery from mouse blood and tissues spiked with micronized C60 exceeds 90%. The method is linear from 0.05 to 200 mg of C60 per liter of blood and from 0.05 to 5.00% of C60 per tissue weight. The limit of detection of the method is 0.1 ng of C60 per injection. This method was applied to mouse blood and tissue samples after intraperitoneal administration of a micronized C60 suspension.

Early effects of C60 Administration in Swiss Mice: A Preliminary Account for In Vivo C60 Toxicity.

Abstract High amounts of micronized C60 have been injected intraperitoneally into Swiss mice. Until the fourteenth day, they were still alive without any behaviour trouble. C60 was well absorbed, and found localized in spleen and liver. Inside the liver, C60 was

A new hexagonal phase of fullerene C60

Abstract A new phase of fullerene C 60 with a simple hexagonal unit cell with 6/mmm symmetry was grown by slowly evaporating solutions of C 60 in dichloromethane. X-ray measurements reveal that the c / a ratio is 1.616 at 298 K and increases as temperature decreases. At low temperature, it seems to extrapolate to 1.633, the ideal ratio for a close-packed hexagonal lattice. The unit cell volume which is higher than that of the usual cubic C 60 phases at high temperature decreases near 90 K. A structural model is proposed according to which a 3-fold molecular axis is parallel to the 6-fold crystallographic z -axis. This suggests that the molecules could reorient around this axis at high temperature.

Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children

Compelling evidence shows that fine particulate matters (PMs) from air pollution penetrate lower airways and are associated with adverse health effects even within concentrations below those recommended by the WHO. A paper reported a dose-dependent link between carbon content in alveolar macrophages (assessed only by optical microscopy) and the decline in lung function. However, to the best of our knowledge, PM had never been accurately characterized inside human lung cells and the most responsible components of the particulate mix are still unknown. On another hand carbon nanotubes (CNTs) from natural and anthropogenic sources might be an important component of PM in both indoor and outdoor air. We used high-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy to characterize PM present in broncho-alveolar lavage-fluids (n = 64) and inside lung cells (n = 5 patients) of asthmatic children. We show that inhaled PM mostly consist of CNTs. These CNTs are present in all examined samples and they are similar to those we found in dusts and vehicle exhausts collected in Paris, as well as to those previously characterized in ambient air in the USA, in spider webs in India, and in ice core. These results strongly suggest that humans are routinely exposed to CNTs.

The Influence of C60 Powders On Cultured Human Leukocytes

Abstract In order to check its possible acute toxicity, C60 was incorporated into living human phagocytes. It was observed that C60 has no influence on the survival of human leukocytes.

Photophysical properties of a dendritic methano[60]fullerene octadeca acid and its tert-butyl ester: evidence for aggregation of the acid form in water

The results of a laser flash photolysis investigation of a dendritic methano[60]fullerene octadeca-acid (DA) and its tert-butyl ester (DE) are reported. DE possesses photophysical properties typical of a [60]fullerene mono-adduct with a singlet oxygen quantum yield approaching unity in toluene and a triplet absorption spectrum with a maximum at 710 nm. In methanol DA also possesses properties typical of a [60]fullerene mono-adduct, but in aqueous solution its photophysical behaviour shows a degree of aggregation that is a function of pH and concentration. At pH 7.4 and higher, Coulombic repulsion between de-protonated carboxylate groups reduces the propensity to aggregation and dilute solutions (<∼10−4 M) of DA exhibit typical [60]fullerene mono-adduct behaviour, although the singlet oxygen yield of 0.75 is lower than in methanol (0.93). The rate constant for DA triplet state quenching by oxygen in water (pH 7.4) is relatively low, which reflects shielding of the hydrophobic C60 core by the dendrimer thus reducing the possibility of orbital overlap with oxygen due to restricted diffusion. Aggregation is evident from the UV-VIS absorption spectra at concentrations exceeding ∼10−4 M in water at pH 7.4, beyond which substantial positive deviations from the Beer–Lambert law are observed. In acidic solutions (pH 4.5) the degree of dissociation of the carboxylic acid groups is negligible and the lack of Coulombic repulsion between DA molecules leads to extensive aggregation, even in dilute solutions. In such solutions the singlet oxygen quantum yield is greatly reduced (∼0.13 at pH 4.5).

8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker of oxidative damage in oesophageal cancer patients: lack of association with antioxidant vitamins and polymorphism of hOGG1 and GST

BackgroundThe present report was designed to investigate the origins of elevated oxidative stress measured in cancer patients in our previous work related to a case-control study (17 cases, 43 controls) on oesophageal cancers. The aim was to characterize the relationship between the levels of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG), antioxidant vitamins and genetic susceptibility.Methods8-oxodG was analysed in peripheral blood mononuclear cells (PBMCs) by High Performance Liquid Chromatography with Electrochemical Detection (HPLC-ED). Analysis of gene polymorphisms in GSTM1 and GSTT1 was performed by multiplex PCR and in GSTP1 and hOGG1 by a PCR-RFLP method. Reversed-phase HPLC with UV detection at 294 nm was used to measure vitamins A and E in serum from the same blood samples.ResultsWe observed that in our combined population (cases and control, n = 60), there was no statistically significant correlation between the levels of 8-oxodG and (i) the serum concentration of antioxidant vitamins, vitamin A (P = 0.290) or vitamin E (P = 0.813), or (ii) the incidence of the Ser 326Cys polymorphic variant (P = 0.637) of the hOGG1 gene. Also, the levels of 8-oxodG were not significantly associated with polymorphisms in metabolite-detoxifying genes, such as GST s, except for the positive correlation with Val/Val GST P1 allele (P < 0.0001).ConclusionsThe weakness of our cohort size notwithstanding, vitamins levels in serum and genetic polymorphisms in the hOGG1 or GST genes do not appear to be important modulators of 8-oxodG levels.