001     281507
005     20251030102702.0
024 7 _ |a 10.3390/ijms26189153
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024 7 _ |a 1661-6596
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037 _ _ |a DZNE-2025-01128
041 _ _ |a English
082 _ _ |a 540
100 1 _ |a Nisar, Hasan
|0 0000-0001-5252-2212
|b 0
245 _ _ |a Effect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure.
260 _ _ |a Basel
|c 2025
|b Molecular Diversity Preservation International
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a Hypoxia-induced radioresistance in non-small cell lung cancer (NSCLC) hinders radiotherapy efficacy. Fractionated schedules exploit reoxygenation between fractions to reverse this resistance, but the effects of post-irradiation reoxygenation remain unclear and may depend on radiation quality. We investigated survival, cell cycle progression, cytokine secretion, and gene expression in hypoxic (1 % O2) and reoxygenated A549 cells irradiated with X-rays or carbon ions. Colony-forming assays revealed an Oxygen Enhancement Ratio (OER) > 1 for both hypoxic and reoxygenated cells after X-rays, indicating persistent radioresistance; carbon ion OER ≈ 1 reflected oxygen-independent cytotoxicity. Hypoxia weakened radiation-induced G2 arrest, and this was unaffected by reoxygenation. IL-6 secretion increased after X-rays and IL-8 after carbon ions exposure; both were enhanced under hypoxia and reoxygenation. RNA sequencing revealed that hypoxia induced a pro-survival, epithelial-to-mesenchymal transition (EMT)-promoting, and immune-evasive transcriptional program, which was largely reversed by reoxygenation but without increased clonogenic killing. These findings indicate that short-term reoxygenation after irradiation can normalize hypoxia-driven transcriptional changes yet does not restore radiosensitivity, supporting the advantage of high-linear energy transfer (LET) carbon ions for targeting resistant hypoxic NSCLC cells.
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650 _ 7 |a DNA double-strand breaks
|2 Other
650 _ 7 |a DNA repair
|2 Other
650 _ 7 |a cell cycle
|2 Other
650 _ 7 |a epithelial–mesenchymal transition
|2 Other
650 _ 7 |a hypoxia
|2 Other
650 _ 7 |a interleukin expression
|2 Other
650 _ 7 |a ionizing radiation
|2 Other
650 _ 7 |a lung cancer
|2 Other
650 _ 7 |a non-small cell lung cancer cells
|2 Other
650 _ 7 |a radioresistance
|2 Other
650 _ 7 |a reoxygenation
|2 Other
650 _ 7 |a survival
|2 Other
650 _ 7 |a Oxygen
|0 S88TT14065
|2 NLM Chemicals
650 _ 7 |a Carbon
|0 7440-44-0
|2 NLM Chemicals
650 _ 7 |a Interleukin-6
|2 NLM Chemicals
650 _ 7 |a Interleukin-8
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: metabolism
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: radiotherapy
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: pathology
|2 MeSH
650 _ 2 |a Carcinoma, Non-Small-Cell Lung: genetics
|2 MeSH
650 _ 2 |a Lung Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Lung Neoplasms: radiotherapy
|2 MeSH
650 _ 2 |a Lung Neoplasms: pathology
|2 MeSH
650 _ 2 |a Lung Neoplasms: genetics
|2 MeSH
650 _ 2 |a Radiation Tolerance: drug effects
|2 MeSH
650 _ 2 |a X-Rays
|2 MeSH
650 _ 2 |a A549 Cells
|2 MeSH
650 _ 2 |a Oxygen: metabolism
|2 MeSH
650 _ 2 |a Oxygen: pharmacology
|2 MeSH
650 _ 2 |a Cell Survival: radiation effects
|2 MeSH
650 _ 2 |a Carbon
|2 MeSH
650 _ 2 |a Epithelial-Mesenchymal Transition: radiation effects
|2 MeSH
650 _ 2 |a Cell Hypoxia: radiation effects
|2 MeSH
650 _ 2 |a Interleukin-6: metabolism
|2 MeSH
650 _ 2 |a Gene Expression Regulation, Neoplastic: radiation effects
|2 MeSH
650 _ 2 |a Interleukin-8: metabolism
|2 MeSH
700 1 _ |a Konda, Bikash
|b 1
700 1 _ |a Roggan, Marie Denise
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700 1 _ |a Labonté, Frederik M
|b 3
700 1 _ |a Arif, Maryam
|b 4
700 1 _ |a Diegeler, Sebastian
|0 0000-0003-3161-0744
|b 5
700 1 _ |a Schmitz, Claudia
|b 6
700 1 _ |a Baumstark-Khan, Christa
|b 7
700 1 _ |a Chevalier, François
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700 1 _ |a Hellweg, Christine E
|0 0000-0002-2223-3580
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770 _ _ |a Molecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment
773 _ _ |a 10.3390/ijms26189153
|g Vol. 26, no. 18, p. 9153 -
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