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000281507 041__ $$aEnglish
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000281507 1001_ $$00000-0001-5252-2212$$aNisar, Hasan$$b0
000281507 245__ $$aEffect of Reoxygenation on Radioresistance of Chronically Hypoxic A549 Non-Small Cell Lung Cancer (NSCLC) Cells Following X-Ray and Carbon Ion Exposure.
000281507 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2025
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000281507 520__ $$aHypoxia-induced radioresistance in non-small cell lung cancer (NSCLC) hinders radiotherapy efficacy. Fractionated schedules exploit reoxygenation between fractions to reverse this resistance, but the effects of post-irradiation reoxygenation remain unclear and may depend on radiation quality. We investigated survival, cell cycle progression, cytokine secretion, and gene expression in hypoxic (1 % O2) and reoxygenated A549 cells irradiated with X-rays or carbon ions. Colony-forming assays revealed an Oxygen Enhancement Ratio (OER) > 1 for both hypoxic and reoxygenated cells after X-rays, indicating persistent radioresistance; carbon ion OER ≈ 1 reflected oxygen-independent cytotoxicity. Hypoxia weakened radiation-induced G2 arrest, and this was unaffected by reoxygenation. IL-6 secretion increased after X-rays and IL-8 after carbon ions exposure; both were enhanced under hypoxia and reoxygenation. RNA sequencing revealed that hypoxia induced a pro-survival, epithelial-to-mesenchymal transition (EMT)-promoting, and immune-evasive transcriptional program, which was largely reversed by reoxygenation but without increased clonogenic killing. These findings indicate that short-term reoxygenation after irradiation can normalize hypoxia-driven transcriptional changes yet does not restore radiosensitivity, supporting the advantage of high-linear energy transfer (LET) carbon ions for targeting resistant hypoxic NSCLC cells.
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000281507 650_7 $$2Other$$aDNA double-strand breaks
000281507 650_7 $$2Other$$aDNA repair
000281507 650_7 $$2Other$$acell cycle
000281507 650_7 $$2Other$$aepithelial–mesenchymal transition
000281507 650_7 $$2Other$$ahypoxia
000281507 650_7 $$2Other$$ainterleukin expression
000281507 650_7 $$2Other$$aionizing radiation
000281507 650_7 $$2Other$$alung cancer
000281507 650_7 $$2Other$$anon-small cell lung cancer cells
000281507 650_7 $$2Other$$aradioresistance
000281507 650_7 $$2Other$$areoxygenation
000281507 650_7 $$2Other$$asurvival
000281507 650_7 $$0S88TT14065$$2NLM Chemicals$$aOxygen
000281507 650_7 $$07440-44-0$$2NLM Chemicals$$aCarbon
000281507 650_7 $$2NLM Chemicals$$aInterleukin-6
000281507 650_7 $$2NLM Chemicals$$aInterleukin-8
000281507 650_2 $$2MeSH$$aHumans
000281507 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: metabolism
000281507 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: radiotherapy
000281507 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: pathology
000281507 650_2 $$2MeSH$$aCarcinoma, Non-Small-Cell Lung: genetics
000281507 650_2 $$2MeSH$$aLung Neoplasms: metabolism
000281507 650_2 $$2MeSH$$aLung Neoplasms: radiotherapy
000281507 650_2 $$2MeSH$$aLung Neoplasms: pathology
000281507 650_2 $$2MeSH$$aLung Neoplasms: genetics
000281507 650_2 $$2MeSH$$aRadiation Tolerance: drug effects
000281507 650_2 $$2MeSH$$aX-Rays
000281507 650_2 $$2MeSH$$aA549 Cells
000281507 650_2 $$2MeSH$$aOxygen: metabolism
000281507 650_2 $$2MeSH$$aOxygen: pharmacology
000281507 650_2 $$2MeSH$$aCell Survival: radiation effects
000281507 650_2 $$2MeSH$$aCarbon
000281507 650_2 $$2MeSH$$aEpithelial-Mesenchymal Transition: radiation effects
000281507 650_2 $$2MeSH$$aCell Hypoxia: radiation effects
000281507 650_2 $$2MeSH$$aInterleukin-6: metabolism
000281507 650_2 $$2MeSH$$aGene Expression Regulation, Neoplastic: radiation effects
000281507 650_2 $$2MeSH$$aInterleukin-8: metabolism
000281507 7001_ $$aKonda, Bikash$$b1
000281507 7001_ $$0P:(DE-2719)9002551$$aRoggan, Marie Denise$$b2$$udzne
000281507 7001_ $$aLabonté, Frederik M$$b3
000281507 7001_ $$aArif, Maryam$$b4
000281507 7001_ $$00000-0003-3161-0744$$aDiegeler, Sebastian$$b5
000281507 7001_ $$aSchmitz, Claudia$$b6
000281507 7001_ $$aBaumstark-Khan, Christa$$b7
000281507 7001_ $$00000-0002-8488-2324$$aChevalier, François$$b8
000281507 7001_ $$00000-0002-2223-3580$$aHellweg, Christine E$$b9
000281507 770__ $$aMolecular Perspectives in Lung Diseases: Pathogenesis, Diagnosis, and Treatment
000281507 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms26189153$$gVol. 26, no. 18, p. 9153 -$$n18$$p9153$$tInternational journal of molecular sciences$$v26$$x1422-0067$$y2025
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