Asynchronous DNA replication detected by fluorescence in situ hybridisation as a possible indicator of genetic damage in human lymphocytes

A. Bras, Cândida Zita Cotrim, I Vasconcelos, João Tiago Praça Nunes Mexia, A Leonard, I Sanzhar, N. B. Akhmatullina, J. Rueff

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The present study aimed to correlate the DNA replication timing of different genes with genetic damage and frequency of cancer. Using a fluorescence in situ hybridisation (FISH) approach, the replication timing of three loci, two human genes possessing transcriptional capability and involved in both the cellular response to genetic damage and cancer development (TP53 and RB1) and the non-coding locus D22S163, was evaluated. The data obtained show that normal human lymphocytes exposed in vitro to known DNA-damaging agents, e.g. H2O2, ionizing radiation and mitomycin C, exhibit an asynchronous replication of the genes TP53 and RB1. In vivo studies were performed in three different populations from Kazakhstan. In two of these populations that are living in polluted areas and have higher cancer mortalities than people living in a control area, a DNA replication behaviour similar to that observed in human lymphocytes exposed in vitro to known genotoxic agents was detected. The results obtained further indicate that DNA damage hampers replication and FISH represents a fast and accurate method of assessing asynchronous replication by providing an important tool to evaluate DNA damage at a populational level.
Original languageEnglish
Pages (from-to)369-375
Number of pages7
JournalOncology Reports
Volume19
Issue number2
Publication statusPublished - 1 Feb 2008

Keywords

  • Genetic damage
  • TP53
  • D22S163
  • DNA replication timing
  • Fluorescence in situ hybridisation
  • RB1

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