Supernatants from quartz dust treated human macrophages stimulate cell proliferation of different human lung cells as well as collagen-synthesis of human diploid lung fibroblasts in vitro

— Human fetal lung fibroblasts (HFL1) were studied in culture to evaluate their potential as a screen for cytotoxicity. The cytotoxic concentrations determined in vitro were compared with established human and animal toxicity data. Confluent monolayers were incubated in the absence or presence of increasing concentrations of test chemicals for 24 hours, and the MTT assay was used to assess toxicity. Inhibitory concentrations were extrapolated from concentration-effect curves after linear regression analysis. Comparison of the cytotoxicity data with rodent lethal concentrations and human lethal concentrations obtained from the testing of 50 chemicals in human lung cells, suggests that the experimental IC50 values are as accurate as predictors of human toxicity as the equivalent toxic blood concentrations derived from rodent LD50 tests. In addition, evaluation of the first 15 chemicals reveals no significant differences between results from continuous cell lines of human and rodent origin. Together with a related battery of tests, cell culture procedures have the potential to supplement or replace current animal protocols in screening chemicals for human toxicity.

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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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