Reactive oxygen and nitrogen species: efficient, selective, and interactive signals during intercellular induction of apoptosis.

During intercellular induction of apoptosis, transformed fibroblasts are specifically eliminated by their nontransformed neighbours. This potential control step of oncogenesis is based on a sophisticated system of interdependencies and interactions of reactive oxygen and nitrogen species. Activated nontransformed effector cells release a novel peroxidase and nitric oxide. Superoxide anions generated extracellularly by transformed cells participate in intercellular signalling and also determine transformed cells as selective targets for intercellular induction of apoptosis. The interaction of these molecules results in two major signalling pathways, which are based on HOCl/hydroxyl radicals and on NO/peroxynitrite. In addition, involvement of nitrylchloride seems to be conceivable in an alternative pathway. Hydrogenperoxide plays a central and ambivalent role by fostering the HOCl/hydroxyl radical pathway and by inhibiting the NO/peroxynitrite pathway. The interaction of ROS and RNS during intercellular induction of apoptosis seems to represent a general signalling concept utilized by several natural antitumor systems.