Condensed chromatin and cell inactivation by single-hit kinetics

J. D. Chapman, C. C. Stobbe, T. Gales, I. J. Das, D. L. Zellmer, S. Biade, Y. Matsumoto

Research output: Contribution to journalArticle

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Abstract

Mammalian cells are extremely sensitive to γ rays at mitosis, the time at which their chromatin is maximally condensed. The radiation-induced killing of mitotic cells is well described by single-hit inactivation kinetics. To investigate if radiation hypersensitivity by single-hit inactivation correlated with chromatin condensation, Chinese hamster ovary (CHO) K1 (wild-type) and xrs-5 (radiosensitive mutant) cells were synchronized by mitotic shake-off procedures and the densities of their chromatin cross sections and their radiosensitivities were measured immediately and 2 h into G1 phase. The chromatin of G1-phase CHO K1 cells was dispersed uniformly throughout their nuclei, and its average density was at least three times less than in the chromosomes of mitotic CHO K1 cells. The α-inactivation coefficient of mitotic CHO K1 cells was ~ 2.0 Gy-1 and decreased ~ 10-fold when cells entered G1 phase. The density of chromatin in CHO xrs-5 cell chromosomes at mitosis was greater than in CHO K1 cell chromosomes, and the radiosensitivity of mitotic CHO xrs-5 cells was the greatest with α = 5.1 Gy-1. In G1 phase, CHO xrs-5 cells were slightly more resistant to radiation than when in mitosis, but a significant proportion of their chromatin was found to remain in condensed form adjacent to the nuclear membrane. These studies indicate that in addition to their known defects in DNA repair and V(D)J recombination, CHO xrs-5 cells may also be defective in some process associated with the condensation and/or dispersion of chromatin at mitosis. Their radiation hypersensitivity could result, in part, from their DNA remaining in compacted form during interphase. The condensation status of DNA in other mammalian cells could define their intrinsic radiosensitivity by single-hit inactivation, the mechanism of cell killing which dominates at the dose fraction size (1.8-2.0 Gy) most commonly used in radiotherapy.

Original languageEnglish (US)
Pages (from-to)433-441
Number of pages9
JournalRadiation Research
Volume151
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

chromatin
ovaries
hamsters
deactivation
Chromatin
inactivation
Chinese hamsters
Cricetulus
kinetics
Ovary
cells
mitosis
interphase
G1 Phase
chromosomes
radiation tolerance
Mitosis
Radiation Tolerance
deoxyribonucleic acid
condensation

ASJC Scopus subject areas

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

Cite this

Chapman, J. D., Stobbe, C. C., Gales, T., Das, I. J., Zellmer, D. L., Biade, S., & Matsumoto, Y. (1999). Condensed chromatin and cell inactivation by single-hit kinetics. Radiation Research, 151(4), 433-441. https://doi.org/10.2307/3579830

Condensed chromatin and cell inactivation by single-hit kinetics. / Chapman, J. D.; Stobbe, C. C.; Gales, T.; Das, I. J.; Zellmer, D. L.; Biade, S.; Matsumoto, Y.

In: Radiation Research, Vol. 151, No. 4, 1999, p. 433-441.

Research output: Contribution to journalArticle

Chapman, JD, Stobbe, CC, Gales, T, Das, IJ, Zellmer, DL, Biade, S & Matsumoto, Y 1999, 'Condensed chromatin and cell inactivation by single-hit kinetics', Radiation Research, vol. 151, no. 4, pp. 433-441. https://doi.org/10.2307/3579830
Chapman JD, Stobbe CC, Gales T, Das IJ, Zellmer DL, Biade S et al. Condensed chromatin and cell inactivation by single-hit kinetics. Radiation Research. 1999;151(4):433-441. https://doi.org/10.2307/3579830
Chapman, J. D. ; Stobbe, C. C. ; Gales, T. ; Das, I. J. ; Zellmer, D. L. ; Biade, S. ; Matsumoto, Y. / Condensed chromatin and cell inactivation by single-hit kinetics. In: Radiation Research. 1999 ; Vol. 151, No. 4. pp. 433-441.
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