title: Excessive Reactive Oxygen Species and Exotic DNA Lesions as an Exploitable Liability.
abstract: Although the terms "excessive reactive oxygen species (ROS)" and "oxidative stress" are widely used, the implications of oxidative stress are often misunderstood. ROS are not a single species but a variety of compounds, each with unique biochemical properties and abilities to react with biomolecules. ROS cause activation of growth signals through thiol oxidation and may lead to DNA damage at elevated levels. In this review, we first discuss a conceptual framework for the interplay of ROS and antioxidants. This review then describes ROS signaling using FLT3-mediated growth signaling as an example. We then focus on ROS-mediated DNA damage. High concentrations of ROS result in various DNA lesions, including 8-oxo-7,8-dihydro-guanine, oxazolone, DNA-protein cross-links, and hydantoins, that have unique biological impacts. Here we delve into the biochemistry of nine well-characterized DNA lesions. Within each lesion, the types of repair mechanisms, the mutations induced, and their effects on transcription and replication are discussed. Finally, this review will discuss biochemically inspired implications for cancer therapy. Several teams have put forward designs to harness the excessive ROS and the burdened DNA repair systems of tumor cells for treating cancer. We discuss inhibition of the antioxidant system, the targeting of DNA repair, and ROS-activated prodrugs.
authors: Department of Chemistry, University of Cincinnati , 404 Crosley Tower, Cincinnati, Ohio 45221-0172, United States.
authors: Safnas F
authors: SF
authors: AbdulSalam
authors: Department of Chemistry, University of Cincinnati , 404 Crosley Tower, Cincinnati, Ohio 45221-0172, United States.
authors: Fathima Shazna
authors: FS
authors: Thowfeik
authors: Department of Chemistry, University of Cincinnati , 404 Crosley Tower, Cincinnati, Ohio 45221-0172, United States.
authors: Edward J
authors: EJ
authors: Merino
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D004249:DNA Damage; D006801:Humans; D017382:Reactive Oxygen Species / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species