Radiosensitivity of human bronchial epithelial cells with genetic alterations
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Tarih
2005
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info:eu-repo/semantics/openAccess
Özet
Amaç: Bu çalışmada, insan bronşiyal epitel hücrelerinin hTERT (insan telomeraz "reverse" transkriptazı), Cdk4 (siklin bağımlı kinaz 4), "knockdown" p53 ve mutant K-ras onkogeni ile enfekte edilmesiyle elde edilen hücre serilerinin hücre kültürü ortamında büyüme hızlarının ve radyoterapiye karşı hassasiyetlerinin karşılaştırılması amaçlanmıştır. Metodlar: İnsan bronş dokusu örneklerinden elde edilen bronşiyal hücreler, öncelikle Cdk4 ve hTERT ile enfekte edilerek ölümsüzleştirildi. Daha sonra bu hücreler, "knockdown" p53, mutant K-ras ve "knockdown" p53 'le birlikte mutant K-ras eksprese eden hücre serilerinin elde edilmesinde kullanıldı. Bulgular: Hem "knockdown" p53, hem de K-ras ekspresyonu gösteren hücrelerin büyüme hızlarının in vitro şartlarda diğer hücre serilerine oranla daha yüksek olduğu ve kontakt inhibisyon özelliklerini kaybettikleri saptandı. Kontrol hücreleri ile Cdk4, hTERT, "knockdown" p53 ve K-ras ile enfekte edilmiş olan hücrelere 1 Gy ile 10 Gy arasında farklı dozlarda radyoterapi uygulandı, 1 hafta sonra canlı kalan hücrelerin oranı belirlendi. Sonuç: Bu çalışmanın sonuçları, hem"knockdown" p53 hem de mutant K-ras ile enfekte edilen bronşiyal epitel hücrelerinin, sadece K-ras veya "knockdown" p53 ile enfekte edilenlere oranla in vitro şartlarda yüksek proliferasyon hızına sahip olduklarını ve ayrıca DNA hasarına yol açan radyoterapiye cevap olarak büyüme duraklamasına girme özelliklerini kaybettiklerini ortaya koymaktadır.
Purpose: To analyze the proliferation rates and the radioscnsitivily of human bronchial epithelial cells (HBECs) with genetic alterations including human telomerase reverse transcriptase (hTERT), Cdk4 (cyclin dependent kinase 4), knockdown p53 and mutant K-ras overexpression. Materials and Methods: HBECs obtained from human bronchus spe¬cimens were placed into short-term culture and were serially transtected with relroviral constructs containing Cdk4 and hTERT, resulting in continuously growing immortalized normal human bronchial epithelial cell lines. These cell lines were used to produce knock-down p53, mutant K-ras and knockdown p53 plus K-ras expressing cell lines; the proliferation rates and the radiosensitivity of these cell lines were evaluated. The control cells and the Cdk4, hTERT, knockdown p53 and K-ras expressing cells were irradiated (1 Gy-10 Gy) and the fraction survival was determined 1 week later. Results: The proliferation rates of the cells expressing both knockdown p53 and K-ras were higher than those of the other cell lines and show a loss of contact inhibition in vitro. The HBECs infected with both knock¬down p53 and mutant K-ras were more radioresistant compared to cells infected with only mutant K-ras or knockdown p53. Conclusion: HBECs expressing knockdown p53 in addition to mutant K-ras have higher proliferation rates and additionally they lose the ability of growth arrest in response to DNA damage signals such as irradiation.
Purpose: To analyze the proliferation rates and the radioscnsitivily of human bronchial epithelial cells (HBECs) with genetic alterations including human telomerase reverse transcriptase (hTERT), Cdk4 (cyclin dependent kinase 4), knockdown p53 and mutant K-ras overexpression. Materials and Methods: HBECs obtained from human bronchus spe¬cimens were placed into short-term culture and were serially transtected with relroviral constructs containing Cdk4 and hTERT, resulting in continuously growing immortalized normal human bronchial epithelial cell lines. These cell lines were used to produce knock-down p53, mutant K-ras and knockdown p53 plus K-ras expressing cell lines; the proliferation rates and the radiosensitivity of these cell lines were evaluated. The control cells and the Cdk4, hTERT, knockdown p53 and K-ras expressing cells were irradiated (1 Gy-10 Gy) and the fraction survival was determined 1 week later. Results: The proliferation rates of the cells expressing both knockdown p53 and K-ras were higher than those of the other cell lines and show a loss of contact inhibition in vitro. The HBECs infected with both knock¬down p53 and mutant K-ras were more radioresistant compared to cells infected with only mutant K-ras or knockdown p53. Conclusion: HBECs expressing knockdown p53 in addition to mutant K-ras have higher proliferation rates and additionally they lose the ability of growth arrest in response to DNA damage signals such as irradiation.
Açıklama
Anahtar Kelimeler
Genel ve Dahili Tıp
Kaynak
Gazi Medical Journal
WoS Q Değeri
Scopus Q Değeri
Cilt
16
Sayı
2
Künye
Dikmen, Z. G., Dikmen, E., Doğan, P. (2005). Radiosensitivity of human bronchial epithelial cells with genetic alterations. Gazi Medical Journal, 16(2), 84 - 87.
