GENO-SİTOTOKSİSİTE ÇALIŞMALARINA SİTOM YAKLAŞIMI

Year 2019, , 261 - 269, 31.07.2019

Ceren Börçek Kasurka

https://doi.org/10.18036/estubtdc.599209

Abstract

ÖZET

 

DNA hasarının
kromozom seviyesinde çalışılması, genetik toksikoloji araştırmalarının temel
dayanaklarındandır. Mikronükleus yöntemi, kromozom hasarını değerlendirmek
amacıyla geliştirilen yöntemlerden biridir. Mikronükleuslar; sentromeri olmayan
kromozom veya kromatid fragmentlerinden ya da anafazda geç kalıp kutuplara göç
edemeyen kromozom veya kromatidlerden oluşan ve telofazda hücre zarı ile
kuşatılarak kardeş hücre çekirdeklerine dahil olmadan sitoplazmada kalan,
çekirdek dışı küçük cisimciklerdir. Bu yöntemde mikronükleusların yanısıra
nükleoplazmik köprüler (NPK) ve nükleer tomurcuklar (NT) değerlendirilebilmekte
ve hücre ölümü ile nükleer bölünme indeksi de ölçülebilmektedir. Disentrik
kromozomların sentromerlerinin farklı kutuplara göç etmesinden orjinlenen NPK,
DNA’nın yanlış onarımının; kromozom rearanjmanının, telomer uç birleşmesinin; NT
ise gen amplifikasyonu ve/veya değişmiş gen dozajının göstergesi olarak
sayılmaktadır. Ayrıca her hücrenin sahip olduğu çekirdek sayısının
değerlendirilerek nükleer bölünme indeksinin hesaplanmasının yanısıra nekrotik
ve apoptotik hücrelerin de belirlenebilmesi mitotik aktivite ve
sitotoksisitenin tayinine olanak sağlamaktadır. Analiz edilebilen tüm bu
parametreler mikronükleus yöntemini genetik kusurların, beslenme
yetersizliklerinin veya ekzojen kaynaklı genotoksinlerin sebep olduğu kromozomal
instabilite fenotipinin ve değişmiş hücresel canlılığın kapsamlı olarak
ölçülebildiği “sitom” yöntemi haline getirmiştir. Bu derlemede mikronükleus
yönteminin genotoksisite çalışmalarındaki yeri ve önemi ile sitom yaklaşımının
bu yönteme kattığı yeniliklere değinilmiştir.

Keywords

Mikronükleus, Sitom, Genotoksisite, Sitotoksisite

CYTOM APPROACH TO GENO-CYTOTOXICITY STUDIES

Abstract

ABSTRACT

 

Working at the chromosomal level of DNA
damage is the mainstay of the genetic toxicology researches. The micronucleus assay is one of the developed methods
to evaluate chromosomal damage. Micronuclei
are non-centromeric chromosomes/chromatids fragments, or chromosomes/chromatids
which lagging in the anaphase and cannot migrate to the poles, located in the
cytoplasm without being included in the sister cell nuclei and surrounded by
cell membranes in telophase. In this method, besides micronuclei, nucleoplasmic
bridges (NPBs) and nuclear buds (NBUDs) can be evaluated, cell death and
nuclear division index (NDI) can be measured. NPBs originated from the
centromeres of dicentric chromosomes
migrating to different poles, are indicative
of DNA mis-repair, chromosome
rearrangement, telomere end-fusions. NBUDs are considered as markers of gene amplification and/or altered
gene dosage. In addition to NDI, establishing to necrotic and apoptotic cells
may allow the determination of mitotic activity and cytotoxicity. All these
analysed parameters have transformed micronucleus method into "cytome" assay by which chromosomal
instability phenotypes and altered cellular viability caused by genetic
defects, nutritional deficiencies, genotoxins from exogenous sources can be
measured comprehensively.
In this review, the place and importance of micronucleus method in genotoxicity
studies and the innovations caused by the cytome approach are mentioned.

Keywords

Micronucleus, Cytome, Genotoxicity, Cytotoxicity

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