Involvement of the nonhomologous end joining DNA repair pathway in the bystander effect for chromosomal aberrations

John B. Little, Hatsumi Nagasawa, Gloria C. Li, David J. Chen

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Cells of mouse knockout cell lines for Ku80 (now known as Xrcc5), Ku70 (now known as G22p1), DNA-PKcs (now known as Prkdc) and PARP (now known as Adprt) were synchronized in G1 phase and exposed to very low fluences of α particles. The frequency of gross chromosomal aberrations was scored at the first postirradiation metaphase. At the two lowest doses examined, aberrations were induced in 4-9% of wild-type cells and 36-55% of Xrcc5-/- cells, whereas only 23% of the nuclei were traversed by an α particle and thus received any radiation exposure. G22p1-/- cells responded similarly to Xrcc5-/- cells, whereas Prkdc-/- and Adprt-/- cells showed an intermediate effect. The frequency of aberrations per nuclear traversal increased approximately 30-fold for Xrcc5-/- and G22p1-/- cells at the lowest mean dose examined (0.17 cGy), compared with 10-fold in Prkdc-/- cells and 3-fold in wild-type cells. Based on these and other findings, we hypothesize that the marked sensitization of repair-deficient bystander cells to the induction of chromosomal aberrations is a consequence of unrejoined DNA double-strand breaks occurring as a result of clustered damage arising from opposed oxidative lesions and single-strand breaks.

Original languageEnglish (US)
Pages (from-to)262-267
Number of pages6
JournalRadiation Research
Volume159
Issue number2
DOIs
StatePublished - Feb 1 2003

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DNA End-Joining Repair
Bystander Effect
chromosome aberrations
DNA repair
Chromosome Aberrations
aberration
deoxyribonucleic acid
cells
strands
knockout mice
dosage
radiation dosage
Double-Stranded DNA Breaks
G1 Phase
cultured cells
DNA
Metaphase
lesions
metaphase
Knockout Mice

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation

Cite this

Involvement of the nonhomologous end joining DNA repair pathway in the bystander effect for chromosomal aberrations. / Little, John B.; Nagasawa, Hatsumi; Li, Gloria C.; Chen, David J.

In: Radiation Research, Vol. 159, No. 2, 01.02.2003, p. 262-267.

Research output: Contribution to journalArticle

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