Cytotoxic and genotoxic potential of dopamine

A variety of in vitro and in vivo studies demonstrate that dopamine is a to xic molecule that may contribute to neurodegenerative disorders such as Par kinson's disease and ischemia-induced striatal damage. While much attention has focused on the fact that the metabolism of dopamine produces reactive oxygen species (peroxide, superoxide, and hydroxyl radical), growing eviden ce suggests that the neurotransmitter itself may play a direct role in the neurodegenerative. process. Oxidation of the dopamine molecule produces a r eactive quinone moiety that is capable of covalently modifying and damaging cellular macromolecules, This quinone formation occurs spontaneously, can be accelerated by metal ions (manganese or iron), and also arises from sele cted enzyme-catalyzed reactions. Macromolecular damage, combined with incre ased oxidant stress, may trigger cellular responses that eventually lead to cell death. Reactive quinones have long been known to represent environmen tal toxicants and, within the context of dopamine metabolism, may also play a role in pathological processes associated with neurodegeneration. The pr esent discussion will review the oxidative metabolism of dopamine and descr ibe experimental evidence suggesting that dopamine quinone may contribute t o the cytotoxic and genotoxic potential of this essential neurotransmitter. (C) 1999 Wiley-Liss, Inc.