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Vinkristinin Uyardığı Apoptozis Üzerine β-Karoten ve Folik Asitin Etkileri

The Effects of Beta-Carotene and Folic Acid on Vincristine-Induced Apoptosis

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Abstract (2. Language): 
Background: A chemotherapeutic agent, vincristine, inhibits spindle fiber formation in both the neoplastic and normal cells. Reversal of apoptotic effects may be exerted by folic acid and beta-carotene addition in vitro. In this study, we aimed to investigate the effects of folic acid and beta-carotene added alone or together on vincristine induced apoptosis in human multiple myeloma cell line ARH77 and human chronic myeloid leukemia cell line K562 cultures. Materials and Methods: Apoptosis was induced by 10-5M vincristine added to the cultures for 24, 48 and 72 hours. Folic acid and beta-carotene were added alone or together in 10-3 M and 10-7M respectively. Cell viability of every culture was determined after which at least 500 cells were analyzed for apoptotic features. Statistical comparisons of ratios were made with two proportion z test. Results: In ARH77 cells, no significant decrease in apoptotic cell ratios were determined after folic acid and betacarotene addition alone or together (p >0.05). Whereas, in K562 cells, after incubation with vincristine for 24 hours, apoptotic cell ratios were significantly reduced by folic acid and beta-carotene treatment one at a time or together (p <0.05). Conclusion: Reversal of apoptotic effects is dependent on type and metabolic activity of the target cells as well as the induction mechanism of the agent used.
Abstract (Original Language): 
Amaç: Bir kemoterapötik ajan olan vinkristin, iğ iplikçiklerinin oluşumunu hem neoplastik hem normal hücrelerde engellemektedir. Daha önce yapılan çalışmalarda farklı kemoterapötik ajanlarla uyarılan apoptozisin, ortama folik asit ve β-karoten eklenmesi ile in vitro olarak geri dönüşümü gösterilmiştir. Bu çalışmada insan multiple myeloma (MM) hücre dizisi ARH77 ve insan kronik myeloid lösemi (KML) hücre dizisi K562 kültürlerinde vinkristinin uyardığı apoptozise folik asit ve β-karotenin tek tek ve birlikte etkilerinin araştırılması amaçlanmıştır. Gereç ve Yöntem: İnsan MM hücre dizisi ARH77 ve insan KML hücre dizisi K562 standart hücre kültürü koşullarında üretilerek 24, 48 ve 72 saat süre ve 10-5M konsantrasyonda vinkristin ile muamele ederek apoptozis uyarılmıştır. Folik asit ve β-karoten tek tek veya birlikte sırasıyla 10-5 ve 10-7 M konsantrasyonlarda eklenerek etkileri izlenmiştir. Her kültürden canlı hücre oranı belirlendikten sonra, en az 500 hücre apoptotik bulgular açısından analiz edilmiştir. İstatistiksel analizler iki oran z testi ile yapılmıştır. Bulgular: ARH77 hücrelerinde vinkristinin indüklediği apoptotik hücre oranlarında folik asit ve β-karotenin tek tek veya birlikte eklenmesiyle anlamlı azalma belirlenmemiştir (p>0.05). K562 hücrelerinde ise 24 saat süreyle uygulanan vinkristinin indüklediği apoptozis hem folik asit hem de β-karotenin tek tek veya birlikte eklenmesiyle istatistiksel olarak anlamlı düzeyde azalmıştır (p<0.05).
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