Altered growth and radiosensitivity in neural precursor cells subjected to oxidative stress

Purpose: To determine whether changes in oxidative stress could enhance the sensitivity of neural precursor cells to ionizing radiation. Materials and methods: Two strategies were used whereby oxidative stress was modulated endogenously, through manipulation cell culture density, or exogenously, through direct addition of hydrogen peroxide. Results: Cells subjected to increased endogenous oxidative stress through low-density growth routinely exhibited an inhibition of growth following irradiation. However, cells subjected to chronic exogenous oxidative treatments showed increased sensitivity to proton and γ-irradiation compared to untreated controls. Reduced survival of irradiated cultures subjected to oxidizing conditions was corroborated using enzymatic viability assays, and was observed over a range of doses (1 – 5 Gy) and post-irradiation re-seeding densities (20 – 200 K/plate). Conclusions: Collectively our results provide further support for the importance of redox state in the regulation of neural precursor cell function, and suggest that oxidative stress can inhibit the proliferative potential of cells through different mechanisms. This is likely to compromise survival and under conditions where excess exogenous oxidants might predominate, sensitivity to irradiation may be enhanced.

[1]  J. Fike,et al.  Efficient Production of Reactive Oxygen Species in Neural Precursor Cells after Exposure to 250 MeV Protons , 2005, Radiation research.

[2]  J. Fike,et al.  High-LET Radiation Induces Inflammation and Persistent Changes in Markers of Hippocampal Neurogenesis , 2005, Radiation research.

[3]  A. Cogoli,et al.  Hypergravity promotes cell proliferation , 1983, Experientia.

[4]  D. Peehl,et al.  Redox modulation of human prostate carcinoma cells by selenite increases radiation-induced cell killing. , 2005, Free radical biology & medicine.

[5]  J. Fike,et al.  Cell-density-dependent regulation of neural precursor cell function. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[6]  S. Vandenberg,et al.  Indicators of Hippocampal Neurogenesis are Altered by 56Fe-Particle Irradiation in a Dose-Dependent Manner , 2004, Radiation research.

[7]  S. Vandenberg,et al.  Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice , 2004, Experimental Neurology.

[8]  Jacob Raber,et al.  Radiation-Induced Cognitive Impairments are Associated with Changes in Indicators of Hippocampal Neurogenesis , 2004, Radiation research.

[9]  J. Fike,et al.  Radiation Response of Neural Precursor Cells: Linking Cellular Sensitivity to Cell Cycle Checkpoints, Apoptosis and Oxidative Stress , 2004, Radiation research.

[10]  M. Monje,et al.  Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. , 2003, Cancer research.

[11]  A. Bravard,et al.  Persistent oxidative stress after ionizing radiation is involved in inherited radiosensitivity. , 2003, Free radical biology & medicine.

[12]  C. Limoli,et al.  Induction of Chromosomal Instability by Chronic Oxidative Stress 1 , 2022 .

[13]  R. Aft,et al.  2-Deoxy-D-glucose-induced cytotoxicity and radiosensitization in tumor cells is mediated via disruptions in thiol metabolism. , 2003, Cancer research.

[14]  W. Morgan,et al.  Persistent oxidative stress in chromosomally unstable cells. , 2003, Cancer research.

[15]  C. Koch,et al.  Radiation Response of Cells during Altered Protein Thiol Redox , 2003, Radiation research.

[16]  L. Oberley,et al.  Radiation-Induced Adaptive Responses Dismutase-Mediated Gene Expression in Manganese Superoxide , 2002 .

[17]  M. Akashi,et al.  Role of reactive oxygen species in cells overexpressing manganese superoxide dismutase: mechanism for induction of radioresistance. , 2002, Molecular cancer research : MCR.

[18]  T. Stein.  Space flight and oxidative stress. , 2002, Nutrition.

[19]  C. Wade,et al.  Resting energy expenditure of rats acclimated to hypergravity. , 2002, Aviation, space, and environmental medicine.

[20]  M. Monje,et al.  Irradiation induces neural precursor-cell dysfunction , 2002, Nature Medicine.

[21]  R. Schmidt-Ullrich,et al.  Ionizing radiation-induced, mitochondria-dependent generation of reactive oxygen/nitrogen. , 2001, Cancer research.

[22]  Y. Shiloh,et al.  Elevated Cu/Zn‐SOD exacerbates radiation sensitivity and hematopoietic abnormalities of Atm‐deficient mice , 2001, The EMBO journal.

[23]  R. Curi,et al.  Walker‐256 tumor growth causes oxidative stress in rat brain , 2001, Journal of neurochemistry.

[24]  A. Diamond,et al.  Radiosensitivity of Mammalian Cell Lines Engineered to Overexpress Cytosolic Glutathione Peroxidase , 2001, Radiation research.

[25]  Bu-Yeo Kim,et al.  Effects of reactive oxygen species on proliferation of Chinese hamster lung fibroblast (V79) cells. , 2001, Free radical biology & medicine.

[26]  G. Badhwar.  Radiation measurements on the International Space Station. , 2001, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[27]  J Kiefer,et al.  Space radiation research in the new millenium--from where we come and where we go. , 2001, Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics.

[28]  P. Chan,et al.  Free radical pathways in CNS injury. , 2000, Journal of neurotrauma.

[29]  M. Pecaut,et al.  Combined effects of space flight factors and radiation on humans. , 1999, Mutation research.

[30]  S. Love.  Oxidative Stress in Brain Ischemia , 1999, Brain pathology.

[31]  Kenneth J. Smith,et al.  Demyelination: The Role of Reactive Oxygen and Nitrogen Species , 1999, Brain pathology.

[32]  A. Alavi,et al.  Changes in the central nervous system during long-duration space flight: implications for neuro-imaging. , 1998, Advances in space research : the official journal of the Committee on Space Research.

[33]  L. Stodieck,et al.  Cellular responses to gravity: extracellular, intracellular and in-between. , 1998, Advances in space research : the official journal of the Committee on Space Research.

[34]  M. Duchen,et al.  Interrelationships between astrocyte function, oxidative stress and antioxidant status within the central nervous system , 1997, Progress in Neurobiology.

[35]  R. Floyd,et al.  Protective action of nitrone-based free radical traps against oxidative damage to the central nervous system. , 1997, Advances in pharmacology.

[36]  A. Newberg,et al.  Changes in the central nervous system and their clinical correlates during long-term spaceflight. , 1994, Aviation, space, and environmental medicine.

[37]  N. Roehm,et al.  An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. , 1991, Journal of immunological methods.