High-dose antioxidants may cause abnormalities in stem cells

Author: Chris Kamel, 05/20/10

One hurdle facing the use of lab-grown stem cells for therapeutic or experimental purposes is the accumulation of genetic abnormalities over time. The nature of these changes varies, but some may affect therapeutic usefulness and many mirror changes seen in tumour-forming cells. One of the more difficult variables to change when culturing stem cells is the air they are grown in. Typical lab conditions are 20% (atmospheric) oxygen, much higher than the physiological levels found in tissue (about 1-5%). This oxygen-rich environment can lead to an increased generation of reactive oxygen species (ROS) which are a natural byproduct of metabolism, but also highly reactive and known to cause oxidative damage to DNA and protein. In a recent paper published in the journal Stem Cells, researchers tried to counteract ROS generation with some interesting results.

In the experiments, human cardiac and embryonic stem cells were cultured under both normal and low-oxygen conditions and supplemented with different antioxidant cocktails. The researchers found that compared to those grown in atmospheric oxygen, high doses of antioxidants were successful in reducing reactive oxygen but also resulted in more chromosomal abnormalities and lower levels of DNA repair proteins. In contrast, cells grown under physiological oxygen (5%) had fewer genetic aberrations compared to the other groups, indicating that standard growth conditions are sub-optimal. Other data addressing this question are sparse, though previous research has shown that in a mouse model of cancer, low doses of the antioxidant vitamin E protected against tumour formation while high doses enhanced tumorigenesis.

None of this is to say that people should be throwing away their nutritional supplements. While genetic abnormalities were seen at antioxidant levels similar to those reached in the blood with high-dose supplementation, it’s important to remember that effects on stem cells in a petri dish are different from effects in a human body. It does raise a small red flag and call into question a “more is better” approach, but warrants further study before drawing hard conclusions.

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Chris Kamel

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