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Pharmaceuticals

Goldilocks Effect Could Govern Reactive Oxygen Species

by Celia Henry Arnaud
July 11, 2011 | A version of this story appeared in Volume 89, Issue 28

Reactive oxygen species (ROS) such as superoxides and peroxides are known to be mutagens and cause genetic damage leading to cancer. It turns out that going too far to control ROS can lead to cancer as well, according to an international team led by David A. Tuveson of Cancer Research U.K.’s Cambridge Research Institute, in England (Nature, DOI: 10.1038/nature10189). Tuveson and coworkers discovered that several oncogenes turn on Nrf2, the transcription factor that regulates ROS metabolism, leading to enhanced ROS detoxification and increased tumor formation. The researchers assessed the redox state of cells by measuring the ratio of reduced glutathione to oxidized glutathione, with a higher ratio indicating the presence of fewer ROS, and vice versa. Mice with pancreatic and lung cancer that couldn’t produce Nrf2 had higher ROS levels and experienced decreased tumor development. “It’s possible that high levels of ROS will give you one kind of cancer, such as lymphoma, while overly aggressive detoxification will promote other kinds, such as pancreatic and lung cancer,” says Gina M. DeNicola, lead author on the study. “For the purposes of treatment, restoring ROS levels to that of a ‘normal’ cell—not too high or too low—should inhibit tumo ri genesis.”

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