Role of nitric oxide in the radiation-induced bystander effect.
Cells that are not irradiated but are affected by "stress signal factors" released from irradiated cells are called bystander cells. These cells, as well as directly irradiated ones, express DNA damage-related proteins and display excess DNA damage, chromosome aberrations, mutations, and malignant transformation. This phenomenon has been studied widely in the past 20 years, since its first description by Nagasawa and Little in 1992, and is known as the radiation-induced bystander effect (RIBE). Several factors have been identified as playing a role in the bystander response. This review will focus on one of them, nitric oxide (NO), and its role in the stimulation and propagation of RIBE. The hydrophobic properties of NO, which permit its diffusion through the cytoplasm and plasma membranes, allow this signaling molecule to easily spread from irradiated cells to bystander cells without the involvement of gap junction intercellular communication. NO produced in irradiated tissues mediates cellular regulation through posttranslational modification of a number of regulatory proteins. The best studied of these modifications are S-nitrosylation (reversible oxidation of cysteine) and tyrosine nitration. These modifications can up- or down-regulate the functions of many proteins modulating different NO-dependent effects. These NO-dependent effects include the stimulation of genomic instability (GI) and the accumulation of DNA errors in bystander cells without direct DNA damage.
Department of Radiation Oncology, Massey Cancer Center, Virginia Commonwealth University, VA, USA. Electronic address: vayakovlev@vcu.edu.
Vasily A
VA
Yakovlev
D024201:Bystander Effect / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D003545:Cysteine / Q000378:metabolism; D004249:DNA Damage; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects*; D042822:Genomic Instability / Q000528:radiation effects; D006801:Humans; D016296:Mutagenesis / Q000528:radiation effects; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D026361:Reactive Nitrogen Species / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D014443:Tyrosine / Q000378:metabolism
D009363:Neoplasm Proteins; D026361:Reactive Nitrogen Species; D009569:Nitric Oxide; D014443:Tyrosine; D003545:Cysteine
BRCA1; DNA double-strand break; Gap junction intercellular communication; Genomic instability; Homologous recombination repair; Nitric oxide; Non-homologous end-joining; Radiation-induced bystander effect; Reactive nitrogen species