Oxidative DNA damage by capsaicin and dihydrocapsaicin in the presence of Cu(II)

Capsaicin is the pungent phenolic principle of the Capsicum species, and has shown a wide range of pharmacological properties, including antigenotoxic, antimutagenic, and anticarcinogenic effects. Other studies have, however, shown it to be a tumor promoter and potential mutagen, and a carcinogen, resulting in capsaicin being termed a 'double edged sword'. In the present study, we show that capsaicin is capable of causing strand scission in calf thymus and plasmid DNA in the presence of Cu(II) and that this breakage is mediated by reactive oxygen species, especially the hydroxyl radical. Our results further show that capsaicin can directly generate hydroxyl radicals in the presence of Cu(II). To explore the chemical basis of the DNA breakage reaction by capsaicin, we have compared these properties of capsaicin with its saturated structural analog dihydrocapsaicin (DHC). The rate of DNA degradation, as well as hydroxyl radical formation, was found to be greater in the case of capsaicin. Both capsaicin and DHC are able to reduce Cu(II) to Cu(I), which was shown to be an essential intermediate in the DNA cleavage reaction. Stoichiometric analysis indicated that whereas 1 mol of capsaicin reduced 3 mol of Cu(II), 1 mol of DHC reduced only 2 mol of Cu(II). This explains the,greater activity of capsaicin and also leads to a model for copper binding to the capsaicins. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.