The major contribution of the DNA damage-triggered reactive oxygen species production to cell death: implications for antimicrobial and cancer therapy.

Abstract

Genotoxic agents damage DNA, block DNA replication and provoke cell death. However, there is growing evidence that an important part of their cytotoxicity results from metabolic disturbances induced by treatment. This review article describes how increased production of the reactive oxygen species (ROS) induced by different genotoxic agents contribute to death of prokaryotic and eukaryotic cells. ROS are byproducts of normal cellular functioning. Because ROS are damaging cellular macromolecules, they are constantly eliminated by protective antioxidant mechanisms. However, even a small increase in ROS production may have deleterious consequences because cells possess just enough defensive mechanisms to protect themselves against endogenously produced ROS. Therefore, it may be possible to enhance cytotoxic potential of antimicrobial and anticancer drugs by increasing ROS production or by inhibiting cellular antioxidant systems.