Geant4-DNA Monte Carlo Simülasyonları Kullanılarak Klinik BT Maruziyetinin Neden Olduğu DNA Hasarının Moleküler Düzeyde Değerlendirilmesi

Öz

Bu çalışmada, klinik bilgisayarlı tomografi (BT) maruziyetinden kaynaklanan iyonlaştırıcı radyasyonun biyolojik etkileri Geant4-DNA Monte Carlo simülasyonları kullanılarak moleküler düzeyde araştırılmıştır. DNA hasarı modellemesi, 40 nm kübik voksel içindeki beyin hücresi heterokromatin parçaları için “dnadamage”, “mikrodozimetri” ve “molecularDNA” modelleri kullanılarak gerçekleştirilmiştir. G4EmDNAPhysics fizik modeli kullanılarak DNA ile X-ışını etkileşimleri simüle edilerek tek iplikçik kırılmalarının (SSB'ler), çift iplikçik kırılmalarının (DSB'ler) ve karmaşık kümelenmiş lezyonların kantitatif analizi yapılmıştır. Sonuçlar, klinik BT için tipik olan düşük doz aralığında bile ölçülebilir DNA hasarının meydana geldiğini ve bu hasarın boyutunun doz hesaplama yöntemlerinin doğruluğuna duyarlı olduğunu göstermiştir. Ayrıca çalışma, radyoliz tarafından üretilen reaktif oksijen türlerinin (özellikle hidroksil radikalleri (°OH), süperoksit anyonları (O₂-) ve hidrojen peroksit (H₂O₂)- DNA hasarına aracılık etmedeki kritik rollerini vurgulamıştır. Dimetil sülfoksitin (DMSO) radyasyonun neden olduğu serbest radikalleri temizleme yeteneği, gelecekteki radyoprotektif ajanların geliştirilmesi için değerli bilgiler sağlar. Genel olarak, bu bulgular radyasyon risk değerlendirmesinde moleküler düzeydeki biyolojik etkilerin fiziksel doz ölçütleriyle bütünleştirilmesinin gerekliliğinin altını çizmektedir ve tanısal radyolojik prosedürler sırasında normal dokuların korunmasına yönelik yeni stratejilerin geliştirilmesi için bilgi sağlayabilir.

Anahtar Kelimeler

• Geant4-DNA
• monte carlo simülasyonu
• bilgisayarlı tomografi (BT)
• DNA hasarı

Molecular-Level Assessment of DNA Damage Induced by Clinical CT Exposure Using Geant4-DNA Monte Carlo Simulations

Öz

In this study, the biological effects of ionizing radiation from clinical computed tomography (CT) exposure were investigated at the molecular level. Geant4-DNA Monte Carlo simulations were utilized to facilitate this investigation. A DNA damage modeling study was conducted for brain cell heterochromatin fragments within a 40-nm cubic voxel, employing the "dnadamage," "microdosimetry," and "molecularDNA" models. A quantitative analysis of single-strand breaks (SSBs), double-strand breaks (DSBs), and complex clustered lesions was conducted by simulating X-ray interactions with DNA using the G4EmDNAPhysics physics model. The findings indicated that quantifiable DNA damage transpires even within the low-dose range characteristic of clinical CT, and the magnitude of this damage is contingent on the precision of dose calculation methodologies. Furthermore, the study emphasized the pivotal functions of reactive oxygen species (ROS) produced by radiolysis, specifically hydroxyl radicals (°OH), superoxide anions (O₂⁻), and hydrogen peroxide (H₂O₂), in facilitating DNA damage. The capacity of dimethyl sulfoxide (DMSO) to scavenge radiation-induced free radicals offers significant insights into the development of future radioprotective agents. In summary, the present findings underscore the necessity of integrating molecular-level biological effects with physical dose metrics in radiation risk assessment. This integration may inform the development of novel strategies for the protection of normal tissues during diagnostic radiological procedures.

Anahtar Kelimeler

• Geant4-DNA
• monte carlo simulation
• computed tomography (CT)
• DNA damage

Kaynakça

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