Radyasyon Tarafından İndüklenen Kanser Rat Modelleri
Özet
Kanser, dünya genelinde yüksek morbidite ve mortalite oranlarına sahip olup, vakaların yaklaşık %60'ında radyoterapi (RT) önemli bir tedavi modalitesi olarak uygulanmaktadır. Ancak iyonizan radyasyon, tümör dokusunu hedeflerken sağlıklı dokularda da ciddi lokal ve sistemik komplikasyonlara yol açmaktadır. FDA onaylı tek radyoprotektan olan amifostin, yüksek toksisitesi ve ciddi yan etkileri nedeniyle yaygın kullanılamamaktadır. Bu sınırlamaları aşmak, hastalık mekanizmalarını anlamak ve yeni koruyucu ajanlar geliştirmek amacıyla radyasyon tarafından indüklenen (RI) hayvan modelleri geliştirilmiştir. Lösemi araştırmalarında, düşük spontan insidansı olan RF rat modellerinin yanı sıra, insan AML'sine klinik benzerlik gösteren SJL/J ve genetik değişimlerin izlenebildiği C3H/He alt türleri öne çıkmaktadır. Lenfoma çalışmalarında optimal fraksiyon zamanlaması sunan C57BL, BALB/c ve NFS modelleri kullanılırken; akciğer kanserinde sirkadiyen ritmin etkisini gösteren C3H ve RF modelleri tercih edilmektedir. Meme kanserinde ise stromal mikroçevrenin karsinojenezdeki rolünü aydınlatan BALB/c tüm vücut ışınlaması ve transplantasyon modelleri devrim yaratmıştır. Genel olarak, meme kanseri hariç modellerde erkek ratların tercih edilmesi ve gece ışınlamalarının daha düşük dozlarda etkinlik sağlaması optimum başarı için kritik kriterlerdir.
Cancer remains a leading global health issue with high mortality rates, necessitating radiotherapy (RT) in approximately 60% of cases as a primary treatment modality. Although modern RT targets tumors, ionizing radiation inevitably induces severe local and systemic toxicities in healthy tissues. Amifostine is currently the only FDA-approved radioprotectant, yet its clinical utility is highly restricted due to poor toxicity profiles and severe side effects. To elucidate the underlying pathological mechanisms and develop safer novel agents, radiation-induced (RI) murine models have become indispensable. For leukemogenesis, the RF model provides low spontaneous incidence, while the SJL/J model mirrors human AML, and the C3H model helps trace critical chromosomal aberrations. In lymphoma research, C57BL, BALB/c, and NFS models are standard for evaluating optimal fraction timing. Lung cancer studies utilize C3H and RF strains, which highlight the profound impact of circadian rhythms on tumor induction. Furthermore, BALB/c whole-body irradiation and transplantation models have revolutionized breast cancer research by demonstrating how radiation alters the stromal microenvironment to drive carcinogenesis. Successfully implementing these models requires careful consideration of strain-specific dose-response curves, gender bias favoring males in non-mammary tumors, and nighttime irradiation parameters.
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