Radiobiological effects of flattening filter and flattening filter free radiotherapy x-ray on inflammatory and apoptotic pathways in cardiac and pulmonary tissues in an MCF-7 xenograft breast cancer model


Hacımustafaoğlu F., Aras S., ERZURUMLU Y., Peran B. Ç.

Journal of Radiation Research, cilt.67, sa.4, ss.516-524, 2026 (SCI-Expanded, Scopus)

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 67 Sayı: 4
  • Basım Tarihi: 2026
  • Doi Numarası: 10.1093/jrr/rrag046
  • Dergi Adı: Journal of Radiation Research
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, BIOSIS, Compendex, EMBASE, INSPEC, MEDLINE, Directory of Open Access Journals, Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Technology Collection (ProQuest)
  • Sayfa Sayıları: ss.516-524
  • Anahtar Kelimeler: caspase-3, cleaved caspase-3, MCF-7, NF-κB p65, phospho NF-κB p65
  • Süleyman Demirel Üniversitesi Adresli: Evet

Özet

This study investigated early inflammatory and apoptotic molecular responses in heart and lung tissues following flattening filter (FF) and flattening filter-free (FFF) radiotherapy in a murine MCF-7 xenograft breast cancer model. Mice received a single 20 Gy fraction in FF (400 MU/min) or FFF (1820 MU/min) mode, and cardiopulmonary tissues were analyzed 48 h post-irradiation. Gene expression of Tnf, Il1b, Nfkb and p53 was assessed by RT-qPCR, while NF-κB p65 activation and caspase-3–mediated apoptosis were evaluated by western blot. Both irradiation modalities significantly increased inflammatory cytokine expression and NF-κB signaling compared with controls (P < 0.05), with consistently stronger responses following FFF irradiation. Lung p53 expression increased progressively across tumor-bearing and irradiated groups, indicating enhanced DNA damage signaling, while elevated cleaved caspase-3 levels reflected apoptotic activation, particularly in irradiated groups. Overall, high–dose-rate FFF radiotherapy elicits more pronounced early inflammatory and apoptotic responses in non-target heart and lung tissues than conventional FF delivery, highlighting the importance of incorporating normal tissue radiobiological effects into high-dose-rate radiotherapy strategies.