Altered growth and radiosensitivity in neural precursor cells subjected to oxidative stress.
OBJECTIVE
To determine whether changes in oxidative stress could enhance the sensitivity of neural precursor cells to ionizing radiation.


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 gamma-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.
Limoli
Charles L
CL
Department of Radiation Oncology, University of California, Medical Sciences I, Irvine, California 92697-2695, USA. climoli@uci.edu
Giedzinski
Erich
E
Baure
Jennifer
J
Rola
Radoslaw
R
Fike
John R
JR
D000222:Adaptation, Physiological / Q000502:physiology / Q000528:radiation effects; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D051381:Rats