Our bodies work like busy metropolises, harnessing the power of iron and using hydrogen peroxide (H₂O₂) for dual purposes: cleansing and signaling. However, this system can falter under stress, leading to cellular damage. The interaction of iron and hydrogen peroxide, known as the Fenton reaction, yields hydroxyl radicals, volatile molecules that indiscriminately harm DNA and RNA. Interestingly, the presence of carbon dioxide, infamous for its role in climate change, equips our cells with a defense mechanism: bicarbonate.
A group of chemists from the University of Utah have found that bicarbonate does more than just balance pH levels; it modifies the Fenton reaction within cells. Instead of producing harmful hydroxyl radicals, the reaction creates carbonate radicals that are less damaging to DNA, as stated by Cynthia Burrows, a distinguished chemistry professor and senior author of a study published in PNAS.
“Numerous diseases and conditions involve oxidative stress, including many cancers, all age-related diseases, and various neurological diseases,” Burrows explained. “Our aim is to understand the fundamental chemistry of cells under oxidative stress. We have discovered something about the protective effect of CO₂, which is quite significant.”
In the absence of bicarbonate or CO₂ in experimental DNA oxidation reactions, the process changes. The generated hydroxyl radical is highly reactive and wreaks havoc on DNA. However, Burrows’ team found that bicarbonate, resulting from dissolved CO₂, alters the reaction, producing a less aggressive radical that only affects guanine, one of the four components of our genetic code.
“Bicarbonate, a major buffer within cells, binds to iron and completely transforms the Fenton reaction. This alteration prevents the production of the highly reactive radicals that have been the focus of studies for years,” Burrows said.
These findings could have profound implications for our understanding of oxidative stress and its role in diseases like cancer or aging. They also suggest that many scientists might be conducting experiments that don’t accurately reflect real-world conditions, leading to questionable results.
For instance, cells are often grown in a tissue culture in an incubator set at body temperature, with carbon dioxide levels elevated to 5%. This environment mimics the cells’ natural habitat when metabolizing nutrients. However, this CO₂ concentration is lost when experiments are conducted outside the incubator.
Burrows likens this to opening a can of beer; the CO₂ escapes when cells are removed from the incubator. Therefore, she advises the addition of bicarbonate to yield more reliable results from such experiments.
“Adding bicarbonate to experiments studying DNA oxidation is often overlooked due to the constant release of CO₂. However, to accurately depict DNA damage resulting from normal cellular processes like metabolism, researchers should replicate the actual conditions of the cell and include bicarbonate,” Burrows suggested.
This study could potentially have far-reaching effects on research in various fields. For instance, Burrows’ lab is exploring funding opportunities from NASA to study the impact of CO₂ on people in confined spaces, such as spaceships and submarines.
“Astronauts living and breathing in a capsule release CO₂. The question is, how much CO₂ can they safely endure in their atmosphere? We’ve discovered that, at least in tissue culture, CO₂ can protect against some of the radiation damage that astronauts might encounter. Therefore, moderately higher levels of CO₂ might actually offer a protective effect against radiation, which generates hydroxyl radicals,” Burrows concluded.
