Assessment of genomic instability and proliferation index in cultured lymphocytes of patients with Down syndrome, congenital anomalies and aplastic anaemia

Publication date: Available online 8 June 2018Source: Mutation Research/Genetic Toxicology and Environmental MutagenesisAuthor(s): Alex George, Shriram Venkatesan, Narmada Ashok, Radha Saraswathy, M Prakash HandeAbstractOne hundred and fifteen cases [Down Syndrome (DS) n = 75, Multiple Congenital Anomalies (MCA) n = 15 and Aplastic Anaemia (AA) n = 25], with respect to their nature of predisposition to cancer, were selected for clinical, cytogenetic and cyto-molecular studies to understand the severity of genomic instability according to the nature of the different diseases. Cytogenetic studies included chromosomal aberration (CA) assays and cytokinesis block micronucleus cytome (CBMN-Cyt) assays. In DS, MCA and AA, average frequencies of nuclear anomalies (NA) were 0.015 ± 0.0006, 0.021 ± 0.00123, 0.031 ± 0.00098, respectively and CA were 0.107 ± 0.003, 0.105 ± 0.008, 0.158 ± 0.006, respectively per metaphase. The extent of genomic instability in patients analysed by CBMN-Cyt assays and CA assays was statistically significant in all groups. Comparatively decreased cytokinesis block proliferation index (CBPI) observed in AA patients of 1.59 ± 0.05, support the assumption that decreased levels of CBPI indicate increased genomic damage. Furthermore, we performed peptide nucleic acid fluorescence in situ hybridisation (PNA FISH) analysis to understand the mechanisms behind genomic instability and telomere dysfunction. PNA FISH showe...
Source: Mutation Research Genetic Toxicology and Environmental Mutagenesis - Category: Genetics & Stem Cells Source Type: research