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Agent protects cells from lethal effects of radiation even if given after exposure

nd the treatment helped protect rapidly dividing T cells and B cells in the spleen - immune system cells that are prone to radiation damage - whether it was given 30 minutes before radiation exposure or 30 minutes afterward.

As part of the research, the investigators monitored the levels at which old or damaged cells in the spleen were dying, a process called apoptosis. In a group of control mice that were not exposed to radiation, the researchers determined that 4.7 percent of T cells and 5.1 percent of B cells in the spleen were undergoing apoptosis. This level is considered normal as cells naturally die and are replaced by new ones. After the mice received 5 Grays of whole body radiation, apoptosis increased to 15.6 percent of T cells and 38.7 percent of B cells.

But when the researchers gave TAT-BH4 to the mice prior to whole body radiation, levels of apoptosis dropped significantly, to 8.6 percent of T cells and 16.9 percent of B cells. In mice given TAT-BH4 after radiation exposure, the proportion of cells undergoing apoptosis dropped even further, to 5.7 percent of T cells and 12.3 percent of B cells.

The Washington University approach appears to halt apoptosis by targeting pathways within cells that are far removed, or downstream, from the initial radiation insult. In particular, BH4 is thought to block a release of the electrical charge across the membrane of mitochondria - the powerhouses of cells - a key event in initiating cellular self-destruction. "This gives us a window of opportunity to treat patients and still prevent cells from undergoing programmed cell death," said Richard Hotchkiss, M.D., professor of anesthesiology, medicine and surgery. "We have a lot more work to do, but we are encouraged by these early findings."

Follow-up data suggest that TAT-BH4 is still effective when it is given to irradiated mice one hour after exposure, and the researchers plan further studies to determine how long after exposur
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Contact: Caroline Arbanas
arbanasc@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
8-May-2007


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