A new study helps explain why taking antioxidants may accelerate the growth of early tumors or precancerous lesions in high-risk populations, like smokers. The study was done in mice and further studies in humans will be needed to validate the effect seen here. Antioxidants are chemical compounds that delay some types of cell damage. They do this by preventing the buildup of molecules called reactive oxygen species, or ROS, that can harm cells. Well-known antioxidants include vitamins A, C, and E, as well as some medications. For a long time scientists thought antioxidants could be useful for preventing cancer, but recent clinical trials in humans have hinted that antioxidants do not prevent lung cancer, and may actually increase cancer risk in certain high-risk groups, like smokers. However, the reason for this effect has been unclear. Studying two different antioxidants, vitamin E and a drug called acetylcysteine, Martin Bergö and colleagues found that antioxidants sped up the progression of lung cancer in mice and in human cell lines. The authors used normal daily dietary doses of vitamin E and relatively low doses of acetylcysteine (humans typically received the antioxidant in an inhaled form, but the mice received it by mouth). When mice with early stages of lung cancer were given antioxidants, their tumors accelerated in growth, became more invasive, and killed the mice twice as fast compared to mice with early lung tumors that didn’t receive antioxidants. The antioxidants appear to boost cancer progression by decreasing the amount of a key tumor suppressor protein called p53. "When we knocked out p53 in the mice and in human lung cancer cell lines, the antioxidants had no effect," said Bergö. The antioxidants achieve their deleterious effect by reducing ROS levels in tumors, which in turn reduces levels of DNA damage. The reduced DNA damage lowers levels of p53.The findings suggest that people carrying small undiagnosed tumors in the lungs (possible in anyone, but more likely smokers) should avoid taking extra antioxidants because they may accelerate tumor progression, though more studies are needed. The authors are currently looking into whether these findings apply to other types of cancer. Meanwhile, the jury is still out on the benefits of antioxidants in low-risk populations. "It is still not clear whether or not antioxidants in healthy people may reduce their future risk of lung cancer," Bergö says.