The DNA-Damage Response to γ-Radiation Is Affected by  miR-27a in A549 Cells

Abstract Background The early molecular events in human thyrocytes after 131I exposure have not yet been unravelled. Therefore, we investigated the role of TSH in the 131I-induced DNA damage response and gene expression in primary cultured human thyrocytes. Methods Following exposure of thyrocytes, in the presence or absence of TSH, to 131I (β radiation), γ radiation (3 Gy), and hydrogen peroxide (H2O2), we assessed DNA damage, proliferation, and cell-cycle status. We conducted RNA sequencing to profile gene expression after each type of exposure and evaluated the influence of TSH on each transcriptomic response. Results Overall, the thyrocyte responses following exposure to β or γ radiation and to H2O2 were similar. However, TSH increased 131I-induced DNA damage, an effect partially diminished after iodide uptake inhibition. Specifically, TSH increased the number of DNA double-strand breaks in nonexposed thyrocytes and thus predisposed them to greater damage following 131I exposure. This effect most likely occurred via Gα q cascade and a rise in intracellular reactive oxygen species (ROS) levels. β and γ radiation prolonged thyroid cell-cycle arrest to a similar extent without sign of apoptosis. The gene expression profiles of thyrocytes exposed to β/γ radiation or H2O2 were overlapping. Modulations in genes involved in inflammatory response, apoptosis, and proliferation were observed. TSH increased the number and intensity of modulation of differentially expressed genes after 131I exposure. Conclusions TSH specifically increased 131I-induced DNA damage probably via a rise in ROS levels and produced a more prominent transcriptomic response after exposure to 131I.

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Sulfur Mustard Analog Mechlorethamine (Bis(2-chloroethyl)methylamine) Modulates Cell Cycle Progression via the DNA Damage Response in Human Lung Epithelial A549 Cells

Chemical Research in Toxicology ◽

10.1021/acs.chemrestox.8b00417 ◽

2019 ◽

Vol 32 (6) ◽

pp. 1123-1133 ◽

Cited By ~ 7

Author(s):

Yi-Hua Jan ◽

Diane E. Heck ◽

Debra L. Laskin ◽

Jeffrey D. Laskin

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Damage Response ◽

Cell Cycle Progression ◽

Human Lung ◽

Sulfur Mustard ◽

A549 Cells ◽

Cycle Progression ◽

Lung Epithelial ◽

Damage Response

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Inhibition of DNA‑PK activity sensitizes A549 cells to X‑ray irradiation by inducing the ATM‑dependent DNA damage response

Molecular Medicine Reports ◽

10.3892/mmr.2018.8828 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lina Yang ◽

Xinrui Yang ◽

Yiwei Tang ◽

Defu Zhang ◽

Lijie Zhu ◽

...

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

A549 Cells ◽

X Ray ◽

Damage Response

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Activation of DNA damage response signaling in lung adenocarcinoma A549 cells following oxygen beam irradiation

Mutation Research/Genetic Toxicology and Environmental Mutagenesis ◽

10.1016/j.mrgentox.2011.05.002 ◽

2011 ◽

Vol 723 (2) ◽

pp. 190-198 ◽

Cited By ~ 7

Author(s):

Somnath Ghosh ◽

Himanshi Narang ◽

Asiti Sarma ◽

Harminder Kaur ◽

Malini Krishna

Keyword(s):

Dna Damage ◽

Lung Adenocarcinoma ◽

Dna Damage Response ◽

A549 Cells ◽

Beam Irradiation ◽

Damage Response ◽

Lung Adenocarcinoma A549

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2-Methoxy-6-Acetyl-7-Methyljuglone (MAM) Induces iNOS/NO-mediated DNA Damage Response through Activation of MAPKs Pathways

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180411111950 ◽

2018 ◽

Vol 18 (6) ◽

pp. 903-913 ◽

Cited By ~ 1

Author(s):

Yanan Niu ◽

Renyikun Yuan ◽

Hongwei Gao ◽

Jin-Jian Lu ◽

Qi Kong ◽

...

Keyword(s):

Nitric Oxide ◽

Dna Damage ◽

Cell Death ◽

Dna Damage Response ◽

Cancer Progression ◽

A549 Cells ◽

No Production ◽

Damage Response

Background：There are inconsistent reports about the role of Nitric Oxide (NO) in cancer progression and prevention. Quinones demonstrate significant anti-cancer activities both in vitro and in vivo. Objective： We investigated the effect of 2-methoxy-6-acetyl-7-methyljuglone (MAM), a natural naphthoquinone isolated from Polygonum cuspidatum Sieb. et Zucc, on NO generation and its role in DNA damage in cancer cells. Methods: BEL-7402 and A549 cells were cultured and treated with MAM. The NO generation, DNA damage, and protein expression were determined. Results: MAM induced inducible nitric oxide synthase (iNOS)/NO-mediated DNA damage response through activation of MAPKs pathways. MAM induced DNA damage by activating ATM/Chk2. MAM increased iNOS expression, NO production, and MAPKs (JNK1/2, ERK1/2, and p38MAPK) phosphorylation in concentrationand time- dependent manners. Furthermore, iNOS inhibitor 1400W, iNOS siRNA, and NO scavenger hemoglobin (Hb) could significantly reverse MAM-induced DNA damage, ATM/Chk2 activation, NO production, and cell death. In addition, MAPKs inhibitors (SP600125, U0126, and SB203580) reversed MAM-induced cell death and ATM/Chk2 activation. MAM-induced cell death was partially reversed by 1400W and Hb but enhanced by L-arginine. Conclusion: These results suggested that MAM induced iNOS/NO activation and generation mediated by MAPKs pathways, which resulted in DNA damage.

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