The role of higher-order chromatin structure in the yield and distribution of DNA double-strand breaks in cells irradiated with X-rays or α-particles

H. C. Newman, K. M. Prise*, B. D. Michael

*Corresponding author for this work

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose: To determine whether the non-random distributions of DNA double-strand breaks in cells observed after α-particle irradiation are related to the higher-order structure of the chromatin within the nucleus. Materials and methods: Chinese hamster V79 cells were irradiated as either cellular monolayers, nuclear monolayers with condensed chromatin or nuclear monolayers with relaxed chromatin, and the yields and distribution of DSB measured using two pulsed-field gel electrophoresis protocols capable of separating fragments of 10 kbp to 5.7 Mbp. Results: Using conventional FAR analysis, the effect of isolating nuclear monolayers and changing the chromatin condensation state was less for α-particle irradiated substrates than for X-irradiated ones. When the total number of breaks was measured by separating and quantifying all the fragments produced in the 10 kbp to 5.7 Mbp region, the difference between the observed yields of breaks in X-irradiated cells (7.3 x 10-9 DSB/Gy/bp) relative to α-particles (12.1 x 10-9 DSB/Gy/bp) was largely removed when nuclear monolayers with decondensed chromatin were exposed. The yields, although similar, increased to 44.4 x 10-9 DSB/Gy/bp for X-irradiated decondensed nuclear monolayers and 46.6 x 10-9 DSB/Gy/bp for α-particle irradiated monolayers. However, the α-particle DSB distributions remained non-random. Conclusions: Our results suggest that the non-random distribution of breaks observed in cells with α-particle irradiation, which leads to a high probability for the production of regionally multiply damaged sites, is not related to the underlying chromatin condensation state present in the nucleus.

Original languageEnglish
Pages (from-to)1085-1093
Number of pages9
JournalInternational journal of radiation biology
Volume76
Issue number8
Publication statusPublished - 09 Aug 2000
Externally publishedYes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

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