Adaptive responses to low-dose/low-dose-rate γ rays in normal human fibroblasts

The role of growth architecture and oxidative metabolism

Sonia M. De Toledo, Nesrin Asaad, Perumal Venkatachalam, Ling Li, Roger Howell, Douglas R. Spitz, Edouard Azzam

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

To investigate low-dose/low-dose-rate effects of low-linear energy transfer (LET) ionizing radiation, we used γ-irradiated cells adapted to grow in a three-dimensional architecture that mimics cell growth in vivo. We determined the cellular, molecular and biochemical changes in these cells. Quiescent normal human fibroblasts were irradiated with single acute or chronic doses (1-10 cGy) of 137Cs γ rays. Whereas exposure to an acute dose of 10 cGy increased micronucleus formation, protraction of the dose over 48 h reduced micronucleus frequency to a level similar to or lower than what occurs spontaneously. The protracted treatment also up-regulated the cellular content of the antioxidant glutathione. These changes correlated with modulation of phospho-TP53 (serine 15), a stress marker that was regulated by doses as low as 1 cGy. The DNA damage that occurred after exposure to an acute dose of 10 cGy was protected against in two ways: (1) up-regulation of cellular antioxidant enzyme activity by ectopic overexpression of MnSOD, catalase or glutathione peroxidase, and (2) inhibition of superoxide anion generation by flavin-containing oxidases. These results support a significant role for oxidative metabolism in mediating low-dose radiation effects and demonstrate that cell culture in three dimensions is ideal to investigate radiation-induced adaptive responses. Expression of connexin 43, a constitutive protein of gap junctions, and the G1 checkpoint were more sensitive to regulation by γ rays in cells maintained in a three-dimensional than in a two-dimensional configuration.

Original languageEnglish (US)
Pages (from-to)849-857
Number of pages9
JournalRadiation Research
Volume166
Issue number6
DOIs
StatePublished - Dec 1 2006

Fingerprint

fibroblasts
metabolism
rays
Fibroblasts
dosage
Growth
Antioxidants
Linear Energy Transfer
Connexin 43
Connexins
glutathione
Radiation Effects
antioxidants
Glutathione Peroxidase
Ionizing Radiation
Superoxides
Catalase
Serine
DNA Damage
Glutathione

All Science Journal Classification (ASJC) codes

  • Radiation
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

De Toledo, Sonia M. ; Asaad, Nesrin ; Venkatachalam, Perumal ; Li, Ling ; Howell, Roger ; Spitz, Douglas R. ; Azzam, Edouard. / Adaptive responses to low-dose/low-dose-rate γ rays in normal human fibroblasts : The role of growth architecture and oxidative metabolism. In: Radiation Research. 2006 ; Vol. 166, No. 6. pp. 849-857.
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Adaptive responses to low-dose/low-dose-rate γ rays in normal human fibroblasts : The role of growth architecture and oxidative metabolism. / De Toledo, Sonia M.; Asaad, Nesrin; Venkatachalam, Perumal; Li, Ling; Howell, Roger; Spitz, Douglas R.; Azzam, Edouard.

In: Radiation Research, Vol. 166, No. 6, 01.12.2006, p. 849-857.

Research output: Contribution to journalArticle

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AU - De Toledo, Sonia M.

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