Quantification of ionizing radiation-induced cell death in situ in a vertebrate embryo

Catherine L. Bladen, Melody A. Flowers, Katsuya Miyake, Robert H. Podolsky, John T. Barrett, David J. Kozlowskia, William S. Dynana

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Quantitative studies of radiation cytotoxicity have been performed mostly in cells in culture. For a variety of reasons, however, the response of cells in culture may not reflect the response for cells in situ in a whole organism. We describe here an approach for quantification of radiation-induced cell death in vivo using the transparent embryo of the zebrafish, Danio rerio, as a model vertebrate system. Using this system, we show that the number of TUNEL-positive cells within a defined region increases approximately linearly with radiation dose up to 1 Gy. The results are consistent with predictions of a linear-quadratic model. The use of alternative models, accommodating a response threshold or low-dose hypersensitivity, did not significantly improve the fit to the observed data. Attenuation of the expression of the 80-kDa subunit of Ku, an essential protein for the nonhomologous end-joining pathway of repair, led to a dose reduction of 30- to 34-fold, possibly approaching the limit where each double-strand break causes a lethal hit. In both the Ku80-attenuated and the control embryos, apoptotic cells were distributed uniformly, consistent with a cell-autonomous mechanism of cell death. Together, these results illustrate the potential of the zebrafish for quantitative studies of radiation-induced cell death during embryogenesis and in vivo.

Original languageEnglish (US)
Pages (from-to)149-157
Number of pages9
JournalRadiation research
Volume168
Issue number2
DOIs
StatePublished - Aug 1 2007

Fingerprint

vertebrates
embryos
Ionizing Radiation
ionizing radiation
death
Vertebrates
cell death
embryo (animal)
Zebrafish
Cell Death
Embryonic Structures
Danio rerio
Radiation
radiation
cell culture
cells
dosage
Cell Culture Techniques
In Situ Nick-End Labeling
hypersensitivity

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Cite this

Quantification of ionizing radiation-induced cell death in situ in a vertebrate embryo. / Bladen, Catherine L.; Flowers, Melody A.; Miyake, Katsuya; Podolsky, Robert H.; Barrett, John T.; Kozlowskia, David J.; Dynana, William S.

In: Radiation research, Vol. 168, No. 2, 01.08.2007, p. 149-157.

Research output: Contribution to journalArticle

Bladen, Catherine L. ; Flowers, Melody A. ; Miyake, Katsuya ; Podolsky, Robert H. ; Barrett, John T. ; Kozlowskia, David J. ; Dynana, William S. / Quantification of ionizing radiation-induced cell death in situ in a vertebrate embryo. In: Radiation research. 2007 ; Vol. 168, No. 2. pp. 149-157.
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