It has been proposed that dietary anti-oxidants, such as vitamin C, may be effective in cancer prevention by acting as scavengers of reactive oxygen species (ROS) that induce DNA damage and genotoxin formation. In the June 15 Science, Lee et al. provide evidence that vitamin C can in fact induce the formation of genotoxins (Science 2001, 292:2083-2086). They developed a specialized method, involving liquid chromatography (LC)/atmospheric pressure chemical ionization (APCI)/mass spectrometry (MS)/ultraviolet (UV), to identify DNA-reactive bifunctional electrophiles. They then performed a series of in vitro experiments to examine the effects of vitamin C on the decomposition of lipid hydroperoxides. The vitamin C concentrations they used are comparable with concentrations resulting from oral vitamin C doses of 200mg per day. They found that vitamin C induced the formation of bifunctional electrophiles in the absence of transition metal ions. The authors suggest that these results may explain why vitamin C has not proved effective as a cancer therapeutic agent and suggest that patients in vitamin C chemoprevention studies should be carefully monitored for etheno-dAdo adducts and DNA damage lesions.