scholarly journals Toxicological Characterization of the Inorganic and Organic Arsenic Metabolite Thio-DMAVin Cultured Human Lung Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Marc Bartel ◽  
Franziska Ebert ◽  
Larissa Leffers ◽  
Uwe Karst ◽  
Tanja Schwerdtle
Keyword(s):  
Mode Of Action ◽  
Analytical Techniques ◽  
Lung Cells ◽  
Strand Breaks ◽  
Multinucleated Cells ◽  
Human Lung Cells ◽  
Arsenic Metabolite ◽  
Organic Arsenic ◽  
Dna Strand

We synthesised and toxicologically characterised the arsenic metabolite thiodimethylarsinic acid (thio-DMAV). Successful synthesis of highly pure thio-DMAVwas confirmed by state-of-the-art analytical techniques includingH1-NMR, HPLC-FTMS, and HPLC-ICPMS. Toxicological characterization was carried out in comparison to arsenite and its well-known trivalent and pentavalent methylated metabolites. It comprised cellular bioavailability as well as different cytotoxicity and genotoxicity end points in cultured human A549 lung cells. Of all arsenicals investigated, thio-DMAVexerted the strongest cytotoxicity. Moreover, thio-DMAVdid not induce DNA strand breaks and an increased induction of both micronuclei and multinucleated cells occurred only at beginning cytotoxic concentrations, indicating that thio-DMAVdoes not act via a genotoxic mode of action. Finally, to assess potential implications of thio-DMAVfor human health, further mechanistic studies are urgently necessary to identify the toxic mode of action of this highly toxic, unusual pentavalent organic arsenical.

DNA Single Strand Breaks and Adenine Nucleotide Depletion as Indices of Oxidant Effects on Human Lung Cells

1998 ◽  
Vol 24 (7-8) ◽  
pp. 1088-1096 ◽  
Author(s):  
Tiina R.J Ollikainen ◽  
Kaija I Linnainmaa ◽  
Kari O Raivio ◽  
Vuokko L Kinnula
Keyword(s):  
Human Lung ◽  
Adenine Nucleotide ◽  
Single Strand ◽  
Lung Cells ◽  
Strand Breaks ◽  
Human Lung Cells ◽  
Single Strand Breaks

Quantitation and characterization of leukotriene products released following immunologic stimulation of human lung cells in vitro

CHEST Journal ◽  
1983 ◽  
Vol 83 (5) ◽  
pp. 81S-82 ◽  
Author(s):  
A. G. Leitch ◽  
R. A. Lewis ◽  
E. J. Corey ◽  
K. F. Austen
Keyword(s):  
Human Lung ◽  
Lung Cells ◽  
Human Lung Cells ◽  
Stimulation Of

Repair of deletions and double-strand gaps by homologous recombination in a mammalian in vitro system

1991 ◽  
Vol 11 (1) ◽  
pp. 445-457
Author(s):  
R Jessberger ◽  
P Berg
Keyword(s):  
Dna Sequences ◽  
Kanamycin Resistance ◽  
Double Strand Breaks ◽  
Strand Transfer ◽  
In Vitro System ◽  
Strand Breaks ◽  
Nuclear Extracts ◽  
Dna Strand

We have designed an in vitro system using mammalian nuclear extracts, or fractions derived from them, that can restore the sequences missing at double-strand breaks (gaps) or in deletions. The recombination substrates consist of (i) recipient DNA, pSV2neo with gaps or deletions ranging from 70 to 390 bp in the neo sequence, and (ii) donor DNAs with either complete homology to the recipient (pSV2neo) or plasmids whose homology with pSV2neo is limited to a 1.0- to 1.3-kbp neo segment spanning the gaps or deletions. Incubation of these substrates with various enzyme fractions results in repair of the recipient DNA's disrupted neo gene. The recombinational repair was monitored by transforming recA Escherichia coli to kanamycin resistance and by a new assay which measures the extent of DNA strand transfer from the donor substrate to the recipient DNA. Thus, either streptavidin- or antidigoxigenin-tagged beads are used to separate the biotinylated or digoxigeninylated recipient DNA, respectively, after incubation with the isotopically labeled donor DNA. In contrast to the transfection assay, the DNA strand transfer measurements are direct, quantitative, rapid, and easy, and they provide starting material for the characterization of the recombination products and intermediates. Accordingly, DNA bound to beads serves as a suitable template for the polymerase chain reaction. With appropriate pairs of oligonucleotide primers, we have confirmed that both gaps and deletions are fully repaired, that deletions can be transferred from the recipient DNA to the donor's intact neo sequence, and that cointegrant molecules containing donor and recipient DNA sequences are formed.

scholarly journals Characterization of the proteome and lipidome profiles of human lung cells after low dose and chronic exposure to multiwalled carbon nanotubes

2018 ◽  
Vol 12 (2) ◽  
pp. 138-152 ◽  
Author(s):  
Santosh Phuyal ◽  
Mayes Kasem ◽  
Oskar Knittelfelder ◽  
Animesh Sharma ◽  
Davi de Miranda Fonseca ◽  
...  
Keyword(s):  
Carbon Nanotubes ◽  
Multiwalled Carbon Nanotubes ◽  
Chronic Exposure ◽  
Low Dose ◽  
Human Lung ◽  
Lung Cells ◽  
Multiwalled Carbon ◽  
Human Lung Cells

scholarly journals Influence of the physicochemical features of TiO2 nanoparticles on the formation of a protein corona and impact on cytotoxicity

RSC Advances ◽  
2020 ◽  
Vol 10 (72) ◽  
pp. 43950-43959
Author(s):  
Ozge Kose ◽  
Marion Stalet ◽  
Lara Leclerc ◽  
Valérie Forest
Keyword(s):  
Tio2 Nanoparticles ◽  
Human Lung ◽  
Protein Corona ◽  
Lung Cells ◽  
Human Lung Cells ◽  
Potential Relationship ◽  
Physicochemical Features

Characterization of the formation of the protein corona of TiO2 nanoparticles as a function of the main nanoparticle properties and investigation of potential relationship with the cytotoxicity nanoparticles induce in vitro in human lung cells.

scholarly journals Repair of deletions and double-strand gaps by homologous recombination in a mammalian in vitro system.

1991 ◽  
Vol 11 (1) ◽  
pp. 445-457 ◽  
Author(s):  
R Jessberger ◽  
P Berg
Keyword(s):  
Dna Sequences ◽  
Kanamycin Resistance ◽  
Double Strand Breaks ◽  
Strand Transfer ◽  
In Vitro System ◽  
Strand Breaks ◽  
Nuclear Extracts ◽  
Dna Strand

We have designed an in vitro system using mammalian nuclear extracts, or fractions derived from them, that can restore the sequences missing at double-strand breaks (gaps) or in deletions. The recombination substrates consist of (i) recipient DNA, pSV2neo with gaps or deletions ranging from 70 to 390 bp in the neo sequence, and (ii) donor DNAs with either complete homology to the recipient (pSV2neo) or plasmids whose homology with pSV2neo is limited to a 1.0- to 1.3-kbp neo segment spanning the gaps or deletions. Incubation of these substrates with various enzyme fractions results in repair of the recipient DNA's disrupted neo gene. The recombinational repair was monitored by transforming recA Escherichia coli to kanamycin resistance and by a new assay which measures the extent of DNA strand transfer from the donor substrate to the recipient DNA. Thus, either streptavidin- or antidigoxigenin-tagged beads are used to separate the biotinylated or digoxigeninylated recipient DNA, respectively, after incubation with the isotopically labeled donor DNA. In contrast to the transfection assay, the DNA strand transfer measurements are direct, quantitative, rapid, and easy, and they provide starting material for the characterization of the recombination products and intermediates. Accordingly, DNA bound to beads serves as a suitable template for the polymerase chain reaction. With appropriate pairs of oligonucleotide primers, we have confirmed that both gaps and deletions are fully repaired, that deletions can be transferred from the recipient DNA to the donor's intact neo sequence, and that cointegrant molecules containing donor and recipient DNA sequences are formed.

scholarly journals Genotoxicity and Gene Expression in the Rat Lung Tissue Following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NMs)

2020 ◽  
Author(s):  
Fátima Brandão ◽  
Carla Costa ◽  
Maria João Bessa ◽  
Elise Dumortier ◽  
Florence Debacq-Chainiaux ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amorphous Silica ◽  
Oxidative Dna Damage ◽  
Intratracheal Instillation ◽  
Lung Cells ◽  
Rat Lung ◽  
Strand Breaks ◽  
Silica Nanomaterials ◽  
Dna Strand

Abstract Background: Synthetic amorphous silica (SAS) has been widely used in several industrial and consumer applications for decades and considered safe for humans. However, several reports on the in vitro and in vivo toxicity of amorphous silica nanomaterials (aSiO2 NMs) have been questioning its safety at the nanoscale. In the present study, we investigated the influence of the physicochemical properties (size and surface chemistry) on in vivo pulmonary toxicity using four variants of aSiO2 NMs (SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40). We focused on alterations in lung DNA and protein integrity, and gene expression following intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM.Results: Overall, single intratracheal instillation of all tested NMs did not cause a significant increase of DNA strand breaks in the rat lung. However, a significant but slight increase of oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_ Amino was observed at 21 days post-exposure. In turn, exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in the rat lung cells in every tested dose at 3 days post-exposure, even though in a dose-independent manner. Nevertheless, this damage seems to be repaired since no changes compared to controls were observed in the recovery groups. In STIS, a significant increase of DNA strand breaks in the lung cells of rats exposed to 0.5 mg/m3 of SiO2_7 or to 50 mg/m3 of TiO2_NM105 was observed at both assessed time-points. The gene expression changes detected suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage.Conclusions: Overall, all tested aSiO2 NMs were not associated with marked in vivo toxicity following instillation or STIS. Under our experimental conditions, pyrogenic aSiO2 NMs (SiO2_7 and SiO2_40) showed a higher genotoxic potential compared to colloidal aSiO2 (SiO2_15_Unmod and SiO2_15_Amino). Overall, genotoxicity findings for SiO2_7 from instillation and STIS are concordant, however changes in STIS animals were more permanent/difficult to revert.

OZONE AND NITROGEN DIOXIDE CAUSE DNA STRAND BREAKS IN RAT LUNG CELLS

1991 ◽  
pp. 523-527 ◽  
Author(s):  
Eliezer Bermúdez ◽  
C. Elizabeth Castro ◽  
Mohammad G. Mustafa
Keyword(s):  
Nitrogen Dioxide ◽  
Dna Strand Breaks ◽  
Lung Cells ◽  
Rat Lung ◽  
Strand Breaks ◽  
Dna Strand

scholarly journals Carcinogenic lead chromate induces DNA double-strand breaks in human lung cells

2005 ◽  
Vol 586 (2) ◽  
pp. 160-172 ◽  
Author(s):  
Hong Xie ◽  
Sandra S. Wise ◽  
Amie L. Holmes ◽  
Bo Xu ◽  
Timothy P. Wakeman ◽  
...  
Keyword(s):  
Human Lung ◽  
Double Strand Breaks ◽  
Lung Cells ◽  
Lead Chromate ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Human Lung Cells
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