title: Role of oxidative stress and DNA damage in human carcinogenesis.
abstract: Cells in tissues and organs are continuously subjected to oxidative stress and free radicals on a daily basis. This free radical attack has exogenous or endogenous (intracellular) origin. The cells withstand and counteract this occurrence by the use of several and different defense mechanisms ranging from free radical scavengers like glutathione (GSH), vitamins C and E and antioxidant enzymes like catalase, superoxide dismutase and various peroxidases to sophisticated and elaborate DNA repair mechanisms. The outcome of this dynamic equilibrium is usually the induction of oxidatively induced DNA damage and a variety of lesions of small to high importance and dangerous for the cell i.e. isolated base lesions or single strand breaks (SSBs) to complex lesions like double strand breaks (DSBs) and other non-DSB oxidatively generated clustered DNA lesions (OCDLs). The accumulation of DNA damage through misrepair or incomplete repair may lead to mutagenesis and consequently transformation particularly if combined with a deficient apoptotic pathway. In this review, we present the current status of knowledge and evidence on the mechanisms and involvement of intracellular oxidative stress and DNA damage in human malignancy evolution and possible use of these parameters as cancer biomarkers. At the same time, we discuss controversies related to potential artifacts inherent to specific methodologies used for the measurement of oxidatively induced DNA lesions in human cells or tissues.
authors.affiliation: Department of Biology, Thomas Harriot College of Arts and Sciences, East Carolina University, Greenville, NC 27858, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kryston
authors.forename: Anastassiya B
authors.initials: AB
authors.lastname: Georgiev
authors.forename: Polycarpos
authors.initials: P
authors.lastname: Pissis
authors.forename: Alexandros G
authors.initials: AG
authors.lastname: Georgakilas
mesh_terms: D015415:Biomarkers / Q000032:analysis; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D017382:Reactive Oxygen Species