No drugs exist to protect the public from the high levels of radiation that could be released by a "dirty" bomb or nuclear explosion.
Such excessive exposure typically causes death within weeks as the radiation kills blood cells vital to clotting and fighting infection, along with the stem cells needed to replenish their supply. But now researchers at Washington University School of Medicine in St. Louis report they have developed an agent that protects cells from the lethal effects of radiation, regardless of whether it is given before or after exposure.
Using this agent in mice, the investigators found that the treatment helped shield rapidly dividing cells that are most vulnerable to radiation-induced death, providing proof in principle that it is possible to fend off radiation damage, according to a study published in the April issue of Biochemical and Biophysical Research Communications.
Current treatments for severe radiation exposure, also called acute radiation syndrome, are limited to drugs that boost the production of blood cells and platelets, but this approach is futile if underlying stem cells are also killed off. Moreover, there are no available treatments that can be given after exposure to limit damage to cells.
"We are using an entirely different approach," says Clayton Hunt, Ph.D., of the Department of Radiation Oncology. "Rather than ramp up the production of blood cells, we are trying to prevent radiation-induced cell death from occurring in the first place."
The researchers developed the agent by attaching a portion of the Bcl-xL protein already known to block cell death - a snippet called BH4 - to the HIV protein TAT, which can deftly carry other molecules into cells. They gave the agent intravenously to mice exposed to 5 Grays of radiation. In humans, this level of exposure would cause a sharp drop in blood cells, leaving individuals with an increased risk of infection and bleeding.
They found 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.