Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles—Comparison with NiCl2

Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 µg Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl2. Genotoxicity and cell transformation as well as cellular dose of Ni are also analyzed. Exposure to NiCl2 resulted in the largest number of differentially expressed genes (197), despite limited uptake, suggesting a major role of extracellular receptors and downstream signaling. Gene expression changes for all Ni exposures included genes coding for calcium-binding proteins (S100A14 and S100A2) as well as TIMP3, CCND2, EPCAM, IL4R and DDIT4. Several top enriched pathways for NiCl2 were defined by upregulation of, e.g., interleukin-1A and -1B, as well as Vascular Endothelial Growth Factor A (VEGFA). All Ni exposures caused DNA strand breaks (comet assay), whereas no induction of micronuclei was observed. Taken together, this study provides an insight into Ni-induced toxicity and mechanisms occurring at lower and more realistic exposure levels.

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In vitro synthesis of DNA in nuclei isolated from human lung cells infected with herpes simplex type II virus.

Journal of Virology ◽

10.1128/jvi.15.2.322-331.1975 ◽

1975 ◽

Vol 15 (2) ◽

pp. 322-331 ◽

Cited By ~ 17

Author(s):

A R Kolber

Keyword(s):

Herpes Simplex ◽

Human Lung ◽

Herpes Simplex Type ◽

Lung Cells ◽

Type Ii ◽

In Vitro Synthesis ◽

Human Lung Cells

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Polyphosphate Reverses the Toxicity of the Quasi-Enzyme Bleomycin on Alveolar Endothelial Lung Cells In Vitro

Cancers ◽

10.3390/cancers13040750 ◽

2021 ◽

Vol 13 (4) ◽

pp. 750

Author(s):

Werner E. G. Müller ◽

Meik Neufurth ◽

Shunfeng Wang ◽

Heinz C. Schröder ◽

Xiaohong Wang

Keyword(s):

Dna Damage ◽

Human Lung ◽

Dna Integrity ◽

Lung Cells ◽

Antitumor Antibiotic ◽

Cell Toxicity ◽

Inorganic Polyphosphate ◽

Human Lung Cells ◽

Anti Cancer

The anti-cancer antitumor antibiotic bleomycin(s) (BLM) induces athyminic sites in DNA after its activation, a process that results in strand splitting. Here, using A549 human lung cells or BEAS-2B cells lunc cells, we show that the cell toxicity of BLM can be suppressed by addition of inorganic polyphosphate (polyP), a physiological polymer that accumulates and is released from platelets. BLM at a concentration of 20 µg ml−1 causes a decrease in cell viability (by ~70%), accompanied by an increased DNA damage and chromatin expansion (by amazingly 6-fold). Importantly, the BLM-caused effects on cell growth and DNA integrity are substantially suppressed by polyP. In parallel, the enlargement of the nuclei/chromatin in BLM-treated cells (diameter, 20–25 µm) is normalized to ~12 µm after co-incubation of the cells with BLM and polyP. A sequential application of the drugs (BLM for 3 days, followed by an exposure to polyP) does not cause this normalization. During co-incubation of BLM with polyP the gene for the BLM hydrolase is upregulated. It is concluded that by upregulating this enzyme polyP prevents the toxic side effects of BLM. These data might also contribute to an application of BLM in COVID-19 patients, since polyP inhibits binding of SARS-CoV-2 to cellular ACE2.

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