Significance of reductases in the detoxification of the tobacco-specific carcinogen NNK

Fewer than 20% of habitual smokers develop lung cancer, which suggests that genetic, environmental and nutritional factors contribute to the risk for developing this disease. Recently, five enzymes were shown to initiate the detoxification of nicotine-derived nitrosamine ketone (NNK), the most potent carcinogen present in tobacco. Importantly, four of these enzymes are potently inhibited by glycyrrhetinic acid, the main constituent of licorice. These observations might open novel and hitherto unexplored avenues for the risk assessment and prevention of tobacco-associated lung cancer.