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A constellation of reactive intermediates — electrophiles and free radicals — capable of damaging cellular constituents is generated during normal physiological or pathophysiological processes. The consequences of this damage include enhanced mutation rates, altered cell signaling, and events summarized in other articles in this Perspective series. In many cases, the initially generated reactive intermediates convert cellular constituents into second-generation reactive intermediates capable of inducing further damage. Cells have adapted to the existence of reactive intermediates by the evolution of defense mechanisms that either scavenge these intermediates or repair the damage they cause. High levels of damage can lead to cell death through apoptosis or necrosis. This article provides an overview of DNA and protein damage by endogenous electrophiles and oxidants and an introduction to the consequences of this damage.

Endogenous generation of reactive oxidants and electrophiles and their reactions with DNA and protein