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Titolo:
OXIDATIVE DAMAGE OF MITOCHONDRIAL AND NUCLEAR-DNA INDUCED BY IONIZING-RADIATION IN HUMAN HEPATOBLASTOMA CELLS
Autore:
MORALES A; MIRANDA M; SANCHEZREYES A; BIETE A; FERNANDEZCHECA JC;
Indirizzi:
UNIV BARCELONA,HOSP CLIN & PROV,RADIOTHERAPY SERV,LIVER UNIT,VILLARROEL 170 E-08036 BARCELONA SPAIN UNIV BARCELONA,HOSP CLIN & PROV,RADIOTHERAPY SERV,LIVER UNIT E-08036 BARCELONA SPAIN CSIC,UB,AUGUST PI & SUNER IDIBAPS,INST INVEST BIOMED BARCELONA 08036 SPAIN
Titolo Testata:
International journal of radiation oncology, biology, physics
fascicolo: 1, volume: 42, anno: 1998,
pagine: 191 - 203
SICI:
0360-3016(1998)42:1<191:ODOMAN>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
ELECTRON-TRANSPORT CHAIN; SUPEROXIDE-DISMUTASE; REACTIVE OXYGEN; RAT HEPATOCYTES; INTRACELLULAR GLUTATHIONE; CELLULAR GLUTATHIONE; REDUCED GLUTATHIONE; LIVER-MITOCHONDRIA; GAMMA-IRRADIATION; MAMMALIAN-CELLS;
Keywords:
OXIDATIVE STRESS; GSH; ANTIOXIDANTS; RADIOBIOLOGY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
63
Recensione:
Indirizzi per estratti:
Citazione:
A. Morales et al., "OXIDATIVE DAMAGE OF MITOCHONDRIAL AND NUCLEAR-DNA INDUCED BY IONIZING-RADIATION IN HUMAN HEPATOBLASTOMA CELLS", International journal of radiation oncology, biology, physics, 42(1), 1998, pp. 191-203

Abstract

Purpose: Since reactive oxygen species (ROS) act as mediators of radiation-induced cellular damage, the aim of our studies was to determinethe effects of ionizing radiation on the regulation of hepatocellularreduced glutathione (GSH), survival and integrity of nuclear and mitochondrial DNA (mtDNA) in human hepatoblastoma cells (Hep G2) depleted of GSH prior to radiation. Methods and Materials: GSH, oxidized glutathione (GSSG), and generation of ROS were determined in irradiated (50-500 cGy) Hep G2 cells. Clonogenic survival, nuclear DNA fragmentation,and integrity of mtDNA were assessed in cells depleted of GSH prior to radiation. Results: Radiation of Hep G2 cells (50-400 cGy) resulted in a dose-dependent generation of ROS, an effect accompanied by a decrease of reduced GSH, ranging from a 15% decrease for 50 cGy to a 25% decrease for 400 cGy and decreased GSH/GSSG from a ratio of 17 to a ratio of 7 for controls and from 16 to 6 for diethyl maleate (DEM)-treated cells, Depletion of GSH prior to radiation accentuated the increase of ROS by 40-50%. The depletion of GSH by radiation was apparent in different subcellular sites, being particularly significant in mitochondria, Furthermore, depletion of nuclear GSH to 50-60% of initial valuesprior to irradiation (400 cGy) resulted in DNA fragmentation and apoptosis. Consequently, the survival of Hep G2 to radiation was reduced from 25% of cells not depleted of GSH to 10% of GSH-depleted cells. Fitting the survival rate of cells as a function of GSH using a theoretical model confirmed cellular GSH as a key factor in determining intrinsic sensitivity of Hep G2 cells to radiation. mtDNA displayed an increased susceptibility to the radiation-induced loss of integrity comparedto nuclear DNA, an effect that was potentiated by GSH depletion in mitochondria (10-15% intact mtDNA in GSH-depleted cells vs. 25-30% of repleted cells), Conclusion: GSH plays a critical protective role in maintaining nuclear and mtDNA functional integrity, determining the intrinsic radiosensitivity of Hep G2, Although the DNA repair is a complex process that is not yet completely understood, the protective role of GSH probably does not seem to involve the repair of classical DNA damage but may relate to modification of DNA damage dependent signaling. (C) 1998 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 21:40:03