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PARENT SESSION 1:30 PM to 3:30 PM Sunday, April 21, 2002 Poster Session 4 Oxidative Stress Room: Nevada Exhibition Center
(P09-73) IEC-6 cells exhibit unusual responses to oxidative stress.
Daly, Barbara*,1, Kovacs, Charles1, Evans, Mark1, Arastu, Nermeen1, 1 Division of Radiation Biology and Oncology, Greenville, North Carolina
ABSTRACT- Radiation damage is thought to be associated with the generation of reactive oxygen species(ROS) and, as a result, one would predict that this damage would be modulated by the presence of the free-radical scavenging agent - n-Acetylcysteine (NAC). To test this hypothesis, radiation(xRT) and drug dose response parameters were measured over time using the IEC-6 rat epithelial cell line. Of considerable interest, the dose response of IEC-6 cells to radiation was enhanced, rather than dampened, by short exposures to the antioxidant NAC. Furthermore, this "enhancing" effect of NAC on the radiation response of the IEC-6 cells was observed within 24 hrs of xRT + drug treatment and continued over a 168 hr interval, suggesting that NAC interfered with the subsequent recovery of sublethally damaged cells. In a similar study with ROS-generating hydrogen peroxide, NAC enhanced the dose response to peroxide on IEC-6 cells. To determine whether this somewhat paradoxical response by the IEC-6 cells was the result of an inhibition of proliferation, or an equally probable increase in apoptotic activity, the proliferative status of the IEC-6 cells was established following the drug + xRT treatment. The results support the conclusion that the "enhanced" response of IEC-6 cells to radiation- and chemically-induced oxidative stress in the presence of NAC is associated with an increase in cell loss rather than an inhibition of proliferation, or mitotic delay. A comparison of the IEC-6 response with that of MCF-7 cells underscores the uniqueness of the response of IEC-6 cells to oxidative stress.
KEYWORDS: IEC-6, NAC, ROS
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