In Vitro Chromosome Aberrations in Genotoxicity Assessment (OECD Test No: 473): Applications, Limitations, and Digital-Automated Approaches

Abstract

Genotoxicity is a term that encompasses damage occurring in DNA and/or chromosomes as a result of exposure to various agents. The identification of such damage and the evaluation of genotoxic potential are carried out through genotoxicity tests. The chromosomal aberration (CA) test is a cytogenetic method used to assess chromosomal aberrations that arise spontaneously or are induced by genotoxic agents. This test can be applied to different cell models and provides important information regarding the evaluation of genome integrity. The aim of this review is to examine, based on the literature, the role of the in vitro CA test (Test No.473), as defined and standardized in the OECD test guideline, in genotoxicity assessment, as well as the importance of variability in the application and scoring steps for the reliability and interpretation of results. Furthermore, considering the current digital/semi-automated system used in the CA test, the potential contributions of digital and automation-supported approaches being researched in the field of cytogenetic evaluation to improving workflow, enhancing evaluation consistency, and supporting the scoring process in this test are discussed.

Keywords

• In vitro chromosomal aberrations assay
• OECD Test No. 473
• Genotoxicity
• DNA damage
• Chromosome aberrations
• Automatic image analysis

Genotoksisite Değerlendirmesinde In Vitro Kromozom Anormallikleri Testi (OECD Test No: 473): Uygulamalar, Sınırlılıklar ve Dijital-Otomatik Yaklaşımlar

Abstract

Genotoksisite, DNA’da ve/veya kromozomlarda çeşitli ajanlara maruziyet sonucunda oluşan hasarları kapsayan bir terimdir. Bu hasarların belirlenmesi ve genotoksik potansiyelin değerlendirilmesi genotoksisite testleri aracılığı ile gerçekleştirilmektedir. Kromozom anormallikleri (KA) testi, spontan olarak oluşan ya da genotoksik ajanlar tarafından indüklenen kromozom anormalliklerinin değerlendirilmesinde kullanılan bir sitogenetik yöntemdir. Bu test, farklı hücre modellerine uygulanabilmektedir ve genom bütünlüğünün değerlendirilmesine ilişkin önemli bilgiler sunmaktadır. Bu derlemenin amacı, OECD test kılavuzunda tanımlanan ve standardize edilmiş in vitro KA testinin (Test No. 473) genotoksisite değerlendirmesindeki yerini ve uygulama ile skorlama basamaklarındaki değişkenliğin sonuçların güvenilirliği ve yorumlanması açısından taşıdığı önemi literatür temelinde ele almaktır. Ayrıca, KA testinde kullanılan mevcut dijital/yarı otomatik sistem göz önünde bulundurularak, sitogenetik değerlendirme alanında araştırılan dijital ve otomasyon destekli yaklaşımların bu testte iş akışının iyileştirilmesi, değerlendirme tutarlılığının artırılması ve skorlama sürecinin desteklenmesine yönelik olası katkıları tartışılmaktadır.

Keywords

• In vitro kromozom anormallikleri testi
• OECD Test No. 473
• Genotoksisite
• DNA hasarı
• Kromozom anormallikleri
• Otomatik görüntü analizi

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