The team, led by Cynthia Burrows, a distinguished professor of chemistry, has found that bicarbonate - a product of dissolved CO2 - not only helps regulate pH but also changes the Fenton reaction's output. Instead of forming chaotic hydroxyl radicals, the reaction produces less harmful carbonate radicals, which target DNA more selectively. These findings, published in PNAS, could reshape how oxidative stress is understood in diseases like cancer and aging.
"So many diseases, so many conditions have oxidative stress as a component of disease. That would include many cancers, effectively all age-related diseases, a lot of neurological diseases," Burrows explained. "We're trying to understand cells' fundamental chemistry under oxidative stress. We have learned something about the protective effect of CO2 that I think is really profound."
Burrows' team includes Aaron Fleming, a research associate professor, and doctoral candidate Justin Dingman.
In experiments without bicarbonate or CO2, hydroxyl radicals act unpredictably, damaging DNA broadly. However, when bicarbonate is present, the reaction is directed toward guanine, a specific genetic component.
"Like throwing a dart at the bullseye where G is the center of the target," Burrows said. "Bicarbonate binds to iron, and it completely changes the Fenton reaction. You don't make these super highly reactive radicals that everyone's been studying for decades."
This discovery also highlights potential flaws in laboratory studies. Most researchers grow cells in a CO2-rich incubator to replicate cellular environments. However, CO2 dissipates when experiments are conducted outside these controlled settings, possibly skewing results.
"Just like opening up a can of beer. You release the CO2 when you take your cells out of the incubator. It's like doing experiments with a day-old glass of beer. It's pretty flat. It has lost the CO2, its bicarbonate buffer," Burrows explained.
She suggests researchers must ensure bicarbonate is present to simulate cellular conditions accurately. "These studies suggest that to get an accurate picture of DNA damage that occurs from normal cellular processes like metabolism, researchers need to be careful to mimic the proper conditions of the cell and add bicarbonate, i.e. baking powder!"
The study's implications could extend to space exploration. Burrows' lab is pursuing NASA funding to examine CO2's effects on individuals in confined environments, such as spacecraft. Slightly elevated CO2 levels may shield astronauts from radiation damage by neutralizing hydroxyl radicals.
"You've got astronauts in a capsule living and breathing, and they are exhaling CO2. The problem is how much CO2 can they safely handle in their atmosphere?" Burrows said. "At least in terms of tissue culture, CO2 does have a protective effect from some of the radiation damage these astronauts might experience."
Research Report:CO2 protects cells from iron-Fenton oxidative DNA damage in E. coli and humans
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