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@ARTICLE{Nisar:281507,
      author       = {Nisar, Hasan and Konda, Bikash and Roggan, Marie Denise and
                      Labonté, Frederik M and Arif, Maryam and Diegeler,
                      Sebastian and Schmitz, Claudia and Baumstark-Khan, Christa
                      and Chevalier, François and Hellweg, Christine E},
      title        = {{E}ffect of {R}eoxygenation on {R}adioresistance of
                      {C}hronically {H}ypoxic {A}549 {N}on-{S}mall {C}ell {L}ung
                      {C}ancer ({NSCLC}) {C}ells {F}ollowing {X}-{R}ay and
                      {C}arbon {I}on {E}xposure.},
      journal      = {International journal of molecular sciences},
      volume       = {26},
      number       = {18},
      issn         = {1422-0067},
      address      = {Basel},
      publisher    = {Molecular Diversity Preservation International},
      reportid     = {DZNE-2025-01128},
      pages        = {9153},
      year         = {2025},
      abstract     = {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.},
      keywords     = {Humans / Carcinoma, Non-Small-Cell Lung: metabolism /
                      Carcinoma, Non-Small-Cell Lung: radiotherapy / Carcinoma,
                      Non-Small-Cell Lung: pathology / Carcinoma, Non-Small-Cell
                      Lung: genetics / Lung Neoplasms: metabolism / Lung
                      Neoplasms: radiotherapy / Lung Neoplasms: pathology / Lung
                      Neoplasms: genetics / Radiation Tolerance: drug effects /
                      X-Rays / A549 Cells / Oxygen: metabolism / Oxygen:
                      pharmacology / Cell Survival: radiation effects / Carbon /
                      Epithelial-Mesenchymal Transition: radiation effects / Cell
                      Hypoxia: radiation effects / Interleukin-6: metabolism /
                      Gene Expression Regulation, Neoplastic: radiation effects /
                      Interleukin-8: metabolism / DNA double-strand breaks (Other)
                      / DNA repair (Other) / cell cycle (Other) /
                      epithelial–mesenchymal transition (Other) / hypoxia
                      (Other) / interleukin expression (Other) / ionizing
                      radiation (Other) / lung cancer (Other) / non-small cell
                      lung cancer cells (Other) / radioresistance (Other) /
                      reoxygenation (Other) / survival (Other) / Oxygen (NLM
                      Chemicals) / Carbon (NLM Chemicals) / Interleukin-6 (NLM
                      Chemicals) / Interleukin-8 (NLM Chemicals)},
      cin          = {AG Fuhrmann},
      ddc          = {540},
      cid          = {I:(DE-2719)1011004},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41009714},
      pmc          = {pmc:PMC12470565},
      doi          = {10.3390/ijms26189153},
      url          = {https://pub.dzne.de/record/281507},
}