Reduction and Oxidation Potentials of Genotoxic Estrogen Quinones and Catechols

Lifelong exposure to estrogen is one the strongest epidemiological links for breast and other human cancers. The oxidative metabolism of estrogen generates reactive compounds capable of reacting with and modifying DNA. DNA modification is an initiating event for tumor formation. One class of reactive metabolites resulting from estrogen metabolism is estrogen quinones (EQ). EQ can bind directly to DNA, cause depurination of DNA bases or cause redox cycling that leads to formation of genotoxic free radicals. In order to gain insight into their possible role as redox cycling metabolites, we measure the reduction potentials of two isomeric EQ, E2-2,3-Q and E2-3,4-Q . The first reduction potential of E2-2,3-Q and E2-3.4-Q was measured at -0.275 and -0.495 V, respectively, versus a Ag/AgCl reference electrode. The second reduction potential of E2-2,3-Q and E2-3,4-Q was measured at -0.930 and -0.935 V, respectively. All reduction potentials became more positive (more easily reduced) at lower pH. In addition to the EQ, an amino quinone of E2-3,4-Q was synthesized and characterized by high field NMR. This amino quinone had much higher reduction potentials, which became less negative in acidic medium