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Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells.

ABSTRACT: Combined exposure of single-walled carbon nanotubes (SWCNTs) and trace metal lead (Pb) in ambient air is unavoidable. Most of the previous studies on the toxicity of SWCNTs and Pb have been conducted individually. There is a scarcity of information on the combined toxicity of SWCNTs and Pb in human cells. This work was designed to explore the combined effects of SWCNTs and Pb in human lung epithelial (A549) cells. SWCNTs were prepared through the plasma-enhanced vapor deposition technique. Prepared SWCNTs were characterized by x-ray diffraction, x-ray photoelectron spectroscopy, scanning electron microscopy, and dynamic light scattering. We observed that SWCNTs up to a concentration of 100 µg/mL was safe, while Pb induced dose-dependent (5-100 µg/mL) cytotoxicity in A549 cells. Importantly, cytotoxicity, cell cycle arrest, mitochondrial membrane potential depletion, lipid peroxidation, and induction of caspase-3 and -9 enzymes following Pb exposure (50 µg/mL for 24 h) were efficiently attenuated by the co-exposure of SWCNTs (10 µg/mL for 24 h). Furthermore, generation of Pb-induced pro-oxidants (reactive oxygen species and hydrogen peroxide) and the reduction of antioxidants (antioxidant enzymes and glutathione) were also mitigated by the co-exposure of SWCNTs. Inductively coupled plasma-mass spectrometry results suggest that the adsorption of Pb on the surface of SWCNTs could attenuate the bioavailability and toxicity of Pb in A549 cells. Our data warrant further research on the combined effects of SWCNTs and Pb in animal models.

SUBMITTER: Ahamed M

PROVIDER: S-EPMC7664418 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells.

Ahamed Maqusood M Akhtar Mohd Javed MJ Khan M A Majeed MAM

International journal of environmental research and public health 20201106 21

Combined exposure of single-walled carbon nanotubes (SWCNTs) and trace metal lead (Pb) in ambient air is unavoidable. Most of the previous studies on the toxicity of SWCNTs and Pb have been conducted individually. There is a scarcity of information on the combined toxicity of SWCNTs and Pb in human cells. This work was designed to explore the combined effects of SWCNTs and Pb in human lung epithelial (A549) cells. SWCNTs were prepared through the plasma-enhanced vapor deposition technique. Prepa ...[more]

PMID: 33172159

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Project description:BackgroundEngineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multi-walled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m³, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation.ResultsTwenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17 months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms.ConclusionsThese data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT.

Project description:BACKGROUND:The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). RESULTS:Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 μg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 μg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 μg/mL MWCNT-HT & ND. CONCLUSIONS:Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

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Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells.

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Single-Walled Carbon Nanotubes Attenuate Cytotoxic and Oxidative Stress Response of Pb in Human Lung Epithelial (A549) Cells.

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