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Battle conditions: U.S. Army studies cells under stress
By Adam Marcus

What happens to the body in extreme climates is of great interest to the military. One of the risks soldiers may face is oxygen deprivation, which can kill cells and damage vital organs. With the ultimate goal of helping military men and women survive stressful conditions, U.S. Army researchers and their colleagues have used genomics to study how liver cells respond to the loss of oxygen.

U.S. Army scientists are using genomics to study ways to protect soldiers from the harmful effects of high altitude...

In a new study, they identify nearly 390 genes that switch on or off in the absence of oxygen, or hypoxia.

The list of genes represents a first step in understanding how the human body withstands harsh climates. Further research may benefit not only the military but also civilians, including patients who receive donated organs. During transplant surgery, the supply of oxygen to the organ is temporarily cut off, and understanding the stress response could lead to new ways to protect them from damage.

"It would be great if we could find out what makes an organ resistant to hypoxia, and then promote that before cutting off its oxygen supply and transplanting it," says Lt. Col. Larry Sonna of the U.S. Army Research Institute of Environmental Medicine in Natick, Massachusetts, who led the study. The institute conducts research on how environment, climate and nutrition affect the health and performance of military personnel.

"This research is really quite important for understanding what happens to someone who becomes critically ill," says Craig Lilly, a critical care specialist at Harvard Medical School in Boston and co-author of the study. Doctors in the intensive care unit deal with patients whose cells are starving for oxygen "almost on a daily basis," Lilly says.

...and extreme heat.

As oxygen levels drop, genes involved in the cell's suicide response switch on, the researchers found. Some of these genes could be altered to make tissue more tolerant to hypoxia, says Lilly, who also directs the medical intensive care unit at Boston's Brigham and Women's Hospital.

The new findings seem to contradict long-held dogma among scientists that cells respond the same way to different environmental stressors—from extreme heat to bitter cold. "There is a certain degree of specialization in human cells in responding to stress," says Sonna, whose group reports their findings in Physiological Genomics.

In the study, liver cells were exposed to air with one percent oxygen (Earth's atmosphere is 21 percent oxygen). That level simulates what cells experience during critical illness or ascent to high altitudes. It is also low enough to trigger a cell's defense mechanism against hypoxia.

The researchers identified the genes using 'gene chip' technology. Gene chips are glass slides or microchips spotted with thousands of fragments of DNA. A single chip can reveal which genes in a cell are active under specific conditions.

Future studies will need to sort out which genes are really involved in the stress response, and which ones aren't. The analysis of thousands of genes inevitably leads to false positives. As with any study, says Sonna, the key will be replicating the results in other laboratories and different conditions.

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Sonna, L. et al. Effect of hypoxia on gene expression by human hepatocytes (HepG2). Physiol Genomics 12, 195-207 (February 6, 2003).

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