Değişik kimyasalların drosophila somatik mutasyon ve rekombinasyon testinde (SMART) amifostine ile etkileşimleri
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Date
2006-03-10
Authors
Sevim, Nurdan
Journal Title
Journal ISSN
Volume Title
Publisher
Uludağ Üniversitesi
Abstract
Bu çalışmada antineoplastik ajanlar Gemcitabine ve Fotemustine'ingenotoksikolojik etkileri ile Amifostine'in antimutajenik etkileri, Drosophila kanatSomatik Mutasyon ve Rekombinasyon Testi ile araştırıldı. Bu yöntemde, resesif flare(flr3) ve multiple wing hair (mwh) belirleyici genlerini üçüncü kromozomlarında taşıyanüç günlük larvalar kullanıldı. Larvalar, ilaçların farklı dozlarını içeren besin ile kronikolarak beslendiler. İlaçların etkileri, uygulama sonunda larvalardan çıkan sineklerinkanat imajinel disk hücrelerindeki genetik değişimler (nokta mutasyon, delesyon,ayrılmama, rekombinasyon) sonucunda oluşan mutant trikomlara göre değerlendirildi.Mutant klon değerlendirmeleri, küçük tek tip, büyük tek tip, ikiz klon, toplam mwh vetoplam klon sınıflandırmaları esas alınarak yapıldı.Genotoksik etkisi araştırılan Gemcitabine larvalara 2, 4 ve 8 µg/ml dozlarındabesin aracığıyla verildi. Kanat SMART yöntemiyle Gemcitabine'in mutajenik etkigöstermediği, zayıf rekombinojenik etkisinin olduğu belirlenmiştir.Çalışmada genotoksik etkisi araştırılan diğer ajan Fotemustine de 2, 4 ve 8 µg/mldozlarında larvalara besinle verildi. Drosophila kanat SMART çalışması ile Fotemustinemutajenik ve rekombinojenik etkili bulunmuştur.Çalışmada kullanılan Amifostine larvalara 1, 2 ve 4 µg/ml dozlarında verildi.Uygulamadan elde edilen sonuçlar Amifostine'in herhangi bir mutajenik verekombinojenik etkisinin olmadığını göstermiştir. Ayrıca Gemcitabine veFotemustine'in olası mutajenik ve rekombinojenik etkilerine karşı Amifostine'in hücrekoruyucu etkisi araştırıldı. Larvaların bir grubuna 1 µg/ml Amifostine ve 8 µg/mlGemcitabine, diğer grubuna 1 µg/ml Amifostine ve 8 µg/ml Fotemustine uygulandı.Elde edilen sonuçlar Amifostine'in antimutajenik etkisi olduğunu göstermiştir
In this research, the genotoxic effects of antineoplastic agents Gemcitabine andFotemustine, and antimutagenic properties of Amifostine were studied with Drosophilawing Somatic Mutation and Recombination Test.In this method 3-day old larvae with recessive flare (flr3) and multiple wing hair(mwh) marker genes on their third chromosome were used. Larvae were chronically feddifferent doses of drugs. The effects of drugs were evaluated according to geneticchanges (point mutation, deletion, non-disjuncton, and recombination) in wing imaginaldisc cells that lead to the formation of mutant trichomes. Mutant trichomes evaluationwas based on small single spot, large single spot, twin spot, total mwh and total spotclassification.Gemcitabine, whose genotoxic effects have been studied, were given to larvae indoses of 2, 4 and 8µg/ml. Wing SMART assay showed that Gemcitabine dose not haveany mutagenic effects but has weak recombinogenic effects instead.The other agent Fotemustine, whose genotoxic effects were studied, was givento larvae in 2, 4 and 8 µg/ml doses. Fotemustine was found as mutagenic andrecombinogenic with Drosophila wing SMART method.Amifostine, which was used in this study was given in 1, 2 and 4 µg/ml dosesand the results indicate that Amifostine doesn?t have any mutagenic or recombinogeniceffects. In addition, cytoprotective properties of Amifostine against possible mutagenicand recombinogenic effects of Gemcitabine and Fotemustine were studied. One groupof larvae 1 µg/ml Amifostine and 8 µg/ml Gemcitabine, to another group 1 µg/mlAmifostine and 8µg/ml Fotemustine were given. The results obtained show thatamifostine has antimutagenic effect.
In this research, the genotoxic effects of antineoplastic agents Gemcitabine andFotemustine, and antimutagenic properties of Amifostine were studied with Drosophilawing Somatic Mutation and Recombination Test.In this method 3-day old larvae with recessive flare (flr3) and multiple wing hair(mwh) marker genes on their third chromosome were used. Larvae were chronically feddifferent doses of drugs. The effects of drugs were evaluated according to geneticchanges (point mutation, deletion, non-disjuncton, and recombination) in wing imaginaldisc cells that lead to the formation of mutant trichomes. Mutant trichomes evaluationwas based on small single spot, large single spot, twin spot, total mwh and total spotclassification.Gemcitabine, whose genotoxic effects have been studied, were given to larvae indoses of 2, 4 and 8µg/ml. Wing SMART assay showed that Gemcitabine dose not haveany mutagenic effects but has weak recombinogenic effects instead.The other agent Fotemustine, whose genotoxic effects were studied, was givento larvae in 2, 4 and 8 µg/ml doses. Fotemustine was found as mutagenic andrecombinogenic with Drosophila wing SMART method.Amifostine, which was used in this study was given in 1, 2 and 4 µg/ml dosesand the results indicate that Amifostine doesn?t have any mutagenic or recombinogeniceffects. In addition, cytoprotective properties of Amifostine against possible mutagenicand recombinogenic effects of Gemcitabine and Fotemustine were studied. One groupof larvae 1 µg/ml Amifostine and 8 µg/ml Gemcitabine, to another group 1 µg/mlAmifostine and 8µg/ml Fotemustine were given. The results obtained show thatamifostine has antimutagenic effect.
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Keywords
Gemcitabine, Fotemustine, Amifostine, Drosophila melanogaster, SMART
Citation
Sevim, N. (2006). Değişik kimyasalların drosophila somatik mutasyon ve rekombinasyon testinde (SMART) amifostine ile etkileşimleri. Yayınlanmamış yüksek lisans tezi. Uludağ Üniversitesi Fen Bilimleri Enstitüsü.