Role of oxygen derivatives in the cytotoxicity and DNA damage produced by asbestos on rat pleural mesothelial cells in vitro

AbstractRadioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

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Genotoxicity and inflammatory potential of stainless steel welding fume particles: an in vitro study on standard vs Cr(VI)-reduced flux-cored wires and the role of released metals

Archives of Toxicology ◽

10.1007/s00204-021-03116-x ◽

2021 ◽

Author(s):

Sarah McCarrick ◽

Valentin Romanovski ◽

Zheng Wei ◽

Elin M. Westin ◽

Kjell-Arne Persson ◽

...

Keyword(s):

Dna Damage ◽

In Vitro Study ◽

Human Monocyte ◽

Welding Fumes ◽

Welding Fume ◽

Increased Risk ◽

Underlying Mechanisms ◽

Cored Wires

AbstractWelders are daily exposed to various levels of welding fumes containing several metals. This exposure can lead to an increased risk for different health effects which serves as a driving force to develop new methods that generate less toxic fumes. The aim of this study was to explore the role of released metals for welding particle-induced toxicity and to test the hypothesis that a reduction of Cr(VI) in welding fumes results in less toxicity by comparing the welding fume particles of optimized Cr(VI)-reduced flux-cored wires (FCWs) to standard FCWs. The welding particles were thoroughly characterized, and toxicity (cell viability, DNA damage and inflammation) was assessed following exposure to welding particles as well as their released metal fraction using cultured human bronchial epithelial cells (HBEC-3kt, 5–100 µg/mL) and human monocyte-derived macrophages (THP-1, 10–50 µg/mL). The results showed that all Cr was released as Cr(VI) for welding particles generated using standard FCWs whereas only minor levels (< 3% of total Cr) were released from the newly developed FCWs. Furthermore, the new FCWs were considerably less cytotoxic and did not cause any DNA damage in the doses tested. For the standard FCWs, the Cr(VI) released in cell media seemed to explain a large part of the cytotoxicity and DNA damage. In contrast, all particles caused rather similar inflammatory effects suggesting different underlying mechanisms. Taken together, this study suggests a potential benefit of substituting standard FCWs with Cr(VI)-reduced wires to achieve less toxic welding fumes and thus reduced risks for welders.

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Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells

PLoS ONE ◽

10.1371/journal.pone.0142773 ◽

2015 ◽

Vol 10 (11) ◽

pp. e0142773 ◽

Cited By ~ 2

Author(s):

Claire J. Heath ◽

Maria del Mar Cendra ◽

Alastair Watson ◽

Jean-Philippe Auger ◽

Anish Pandey ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Mesothelial Cells ◽

Pleural Mesothelial Cells

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Lectin Staining of Peritoneal Mesothelial Cells in Vitro

Peritoneal Dialysis International ◽

10.1177/089686089101100403 ◽

1991 ◽

Vol 11 (4) ◽

pp. 307-316 ◽

Cited By ~ 8

Author(s):

J. Thomas Hjelle ◽

Barbara T. Golinska ◽

Diane C. Waters ◽

Kevin R. Steidley ◽

Marcia A. Miller ◽

...

Keyword(s):

Tissue Culture ◽

Cell Surface ◽

Lectin Binding ◽

Mesothelial Cells ◽

Peritoneal Mesothelial Cells ◽

Lectin Staining ◽

Intracellular Vesicles ◽

Intracellular Fluorescence

A survey of lectin-binding specificities present on rodent and human mesothelial cells propagated and maintained in tissue culture was made using fluorescein isothiocynate conjugated (FITC) lectins. Rodent and human cells exhibited cell-associated fluorescence following exposure to the FITC-Iectins from C. ensiformis, T. vulgaris, A. hypogaea, E. cristagalli and B. simplicifolia, but not with lectins from G. max and D. biflorus. Rodent cells were also positive for FITC-M. pomifera lectin binding. Human, but not rodent, cells were positive for FITC T. purpureas lectin binding. Exposure of rabbit mesothelial cells in vitro to FITC-Iectins that bound to the cell surface resulted in the appearance of discrete loci of putatively intracellular fluorescence. Exposure of cells to ferritin-Iabelled T. vulgaris lectin at 37°C for as little as 7.5 minutes resulted in the appearance of ferritin-size particles in intracellular vesicles. These results demonstrate 1. the presence of lectinbinding sites in and on peritoneal mesothelial cells from rodents and humans and 2. a possible role of such sites in mediating the entry of lectin-Iike endogenous molecules into the vacuolar apparatus of these cells.

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SIRT7-mediated ATM deacetylation is essential for its deactivation and DNA damage repair

Science Advances ◽

10.1126/sciadv.aav1118 ◽

2019 ◽

Vol 5 (3) ◽

pp. eaav1118 ◽

Cited By ~ 19

Author(s):

Ming Tang ◽

Zhiming Li ◽

Chaohua Zhang ◽

Xiaopeng Lu ◽

Bo Tu ◽

...

Keyword(s):

Dna Damage ◽

Dna Damage Repair ◽

Class Iii ◽

Ataxia Telangiectasia Mutated ◽

Damage Repair ◽

Damage Response ◽

Late Stages

The activation of ataxia-telangiectasia mutated (ATM) upon DNA damage involves a cascade of reactions, including acetylation by TIP60 and autophosphorylation. However, how ATM is progressively deactivated after completing DNA damage repair remains obscure. Here, we report that sirtuin 7 (SIRT7)–mediated deacetylation is essential for dephosphorylation and deactivation of ATM. We show that SIRT7, a class III histone deacetylase, interacts with and deacetylates ATM in vitro and in vivo. In response to DNA damage, SIRT7 is mobilized onto chromatin and deacetylates ATM during the late stages of DNA damage response, when ATM is being gradually deactivated. Deacetylation of ATM by SIRT7 is prerequisite for its dephosphorylation by its phosphatase WIP1. Consequently, depletion of SIRT7 or acetylation-mimic mutation of ATM induces persistent ATM phosphorylation and activation, thus leading to impaired DNA damage repair. Together, our findings reveal a previously unidentified role of SIRT7 in regulating ATM activity and DNA damage repair.

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