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Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.

ABSTRACT: Chronic oxidative stress has been associated with genomic instability following exposure to ionizing radiation. However, results showing direct causal linkages between specific ROS (reactive oxygen species) and the ionizing radiation-induced mutator phenotype are lacking. The present study demonstrates that ionizing radiation-induced genomically unstable cells (characterized by chromosomal instability and an increase in mutation and gene amplification frequencies) show a 3-fold increase in steady-state levels of hydrogen peroxide, but not superoxide. Furthermore, stable clones isolated from parallel studies showed significant increases in catalase and GPx (glutathione peroxidase) activity. Treatment of unstable cells with PEG-CAT (polyethylene glycol-conjugated catalase) reduced the mutation frequency and mutation rate in a dose-dependent fashion. In addition, inhibiting catalase activity in the stable clones using AT (3-aminotriazole) increased mutation frequency and rate. These results clearly demonstrate the causal relationship between chronic oxidative stress mediated by hydrogen peroxide and the mutator phenotype that persists for many generations following exposure of mammalian cells to ionizing radiation.

SUBMITTER: Dayal D

PROVIDER: S-EPMC2677991 | biostudies-literature | 2008 Jul

REPOSITORIES: biostudies-literature

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Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.

Dayal Disha D Martin Sean M SM Limoli Charles L CL Spitz Douglas R DR

The Biochemical journal 20080701 1

Chronic oxidative stress has been associated with genomic instability following exposure to ionizing radiation. However, results showing direct causal linkages between specific ROS (reactive oxygen species) and the ionizing radiation-induced mutator phenotype are lacking. The present study demonstrates that ionizing radiation-induced genomically unstable cells (characterized by chromosomal instability and an increase in mutation and gene amplification frequencies) show a 3-fold increase in stead ...[more]

PMID: 18352860

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Project description:Autophagy, an evolutionally conserved cellular degradation process, plays critical roles in plant development and stress response. Despite the wealth of information on the vital role of autophagy in responses to environmental stresses, little is known about the regulation of autophagy. In this study, we demonstrated that spermidine (Spd), a kind of polyamine, was involved in the regulation of salt tolerance through activating the expression of ATG (autophagy-related) genes and the formation of autophagosomes in cucumber under salt stress. Furthermore, NADPH oxidase-derived apoplastic H2O2-mediated Spd-induced salt tolerance and autophagy. Exogenous Spd significantly increased the tolerance to salt stress and inhibited the accumulation and ubiquitination of insoluble proteins. Foliar application of Spd promoted the transcript levels of ATG genes and autophagosomes formation. Besides, Spd induced the expression of RBOH (respiratory burst oxidase homolog), and the accumulation of H2O2 both in leaves and roots. However, either pretreatment with dimethylthiourea (DMTU, an H2O2 scavenger) or diphenyleneiodonium chloride (DPI, an inhibitor of NADPH oxidase) reduced Spd-induced accumulation of apoplastic H2O2. Importantly, Spd-induced salt tolerance and autophagy were compromised when plants were pretreated with DMTU or DPI. Furthermore, the silencing of ATG4 and ATG7 reduced Spd-induced salt tolerance and autophagosomes formation. Taken together, these results revealed that RBOH-dependent H2O2 mediated the Spd-induced autophagy and salt tolerance in cucumber.Abbreviations: Asat: light-saturated rate of CO2 assimilation; ATG: autophagy-related; DCF-DA: 2, 7-dichlorofluorescein diacetate; DMTU: dimethylthiourea; DPI: diphenyleneiodonium chloride; DW: dry weight; EL: electrolyte leakage; FW: fresh weight; Fv/Fm: the maximum quantum yield of photosystem II; GFP: green fluorescent protein; MDC: monodansylcadaverine; PDS: phytoene desaturase; PE: phosphatidylethanolamine; PLD: phospholipase D; RBOH: respiratory burst oxidase homolog; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SIN1: salt induced NAC1; Spd: spermidine; TOR: target of rapamycin; VIGS: virus-induced gene silencing.

Dataset Information

Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.

Publications

Hydrogen peroxide mediates the radiation-induced mutator phenotype in mammalian cells.

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