Mechanisms of the formation of radiation-induced chromosomal aberrations

Peter E Bryant, Andrew C Riches, Samantha Y A Terry

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Although much is now known about the mechanisms of radiation-induction of DNA double-strand breaks (DSB), there is less known about the conversion of DSB into chromosomal aberrations. In particular the induction and 'rejoining' of chromatid breaks has been a controversial topic for many years. However, its importance becomes clear in the light of the wide variation in the chromatid break response of human peripheral blood lymphocytes from different individuals when exposed to ionizing radiation, and the elevation of the frequency of radiation-induced chromatid breaks in stimulated peripheral blood lymphocytes of around 40% of breast cancer cases. A common assumption has been that chromatid breaks are merely expansions of initiating DSB, although the classic 'breakage-first' hypothesis (Sax, Ref. 44) was already challenged in the 50's by Revell [30] who maintained that chromatid breaks were formed as a result of an incomplete exchange process initiated by two interacting lesions of an unspecified nature. Here we argue that both these models of chromatid break formation are flawed and we suggest an alternative hypothesis, namely that a radiation-induced DSB initiates an indirect mechanism leading to a chromatid break. This mechanism we suggest involves the nuclear enzyme topoisomerase IIalpha and we present evidence from topoisomerase IIalpha expression variant human cell lines and from siRNA treatment of human cells that supports this hypothesis.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
JournalMutation Research
Volume701
Issue number1
DOIs
Publication statusPublished - 14 Aug 2010

Keywords

  • Antigens, Neoplasm
  • Cell Cycle
  • Cell Line
  • Chromatids
  • Chromosome Aberrations
  • DNA Breaks, Double-Stranded
  • DNA Topoisomerases, Type II
  • DNA-Binding Proteins
  • Humans
  • Lymphocytes
  • Models, Genetic
  • RNA, Small Interfering
  • Radiation Genetics
  • Radiation, Ionizing

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