Journal article
Adaptive Responses to Low-Dose/Low-Dose-Rate γ Rays in Normal Human Fibroblasts: The Role of Growth Architecture and Oxidative Metabolism
Radiation research, Vol.166(6), pp.849-857
12/2006
DOI: 10.1667/RR0640.1
PMID: 17149977
Abstract
de Toledo, S. M., Asaad, N., Venkatachalam, P., Li, L., Howell, R. W., Spitz, D. R. and Azzam, E. I. Adaptive Responses to Low-Dose/Low-Dose-Rate γ Rays in Normal Human Fibroblasts: The Role of Growth Architecture and Oxidative Metabolism. Radiat. Res. 166, 849–857 (2006). 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.
Details
- Title: Subtitle
- Adaptive Responses to Low-Dose/Low-Dose-Rate γ Rays in Normal Human Fibroblasts: The Role of Growth Architecture and Oxidative Metabolism
- Creators
- Sonia M. de Toledo - Rutgers, The State University of New JerseyNesrin Asaad - Rutgers, The State University of New JerseyPerumal Venkatachalam - Rutgers, The State University of New JerseyLing Li - HoldenRoger W. Howell - Rutgers, The State University of New JerseyDouglas R. Spitz - University of IowaEdouard I. Azzam - Rutgers, The State University of New Jersey
- Resource Type
- Journal article
- Publication Details
- Radiation research, Vol.166(6), pp.849-857
- DOI
- 10.1667/RR0640.1
- PMID
- 17149977
- ISSN
- 0033-7587
- eISSN
- 1938-5404
- Number of pages
- 9
- Language
- English
- Date published
- 12/2006
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312984702771
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