Effect of age on the induction of 8-oxo-2′-deoxyguanosine-releasing enzyme in rat liver by γ-ray irradiation

Kaneko, Takao; Tahara, Shoichi; Tanno, Munehiko; Taguchi, Takahiko

doi:10.1016/s0167-4943(02)00056-0

Cited by 16 publications

(11 citation statements)

References 30 publications

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“…Consequently, we used adolescent Fischer rats (31) and started the drug treatment at 0 or 2 weeks after irradiation for comparison to our previous studies that used young adult rats with treatment started at 1 week post irradiation. (10, 32). We terminated treatment with both agents at 28 weeks, but extended the time of analysis to 48 weeks to strengthen our previous findings that showed stopping the treatment at 28 weeks did not decrease the mitigating efficacy measured at late times.…”

Section: Introductionmentioning

confidence: 99%

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

et al. 2012

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Exposure of civilian populations to radiation due to accident, war or terrorist act is an increasing concern. The lung is one of the more radiosensitive organs that may be affected in people receiving partial-body irradiation and radiation injury in lung is thought to be associated with the development of a prolonged inflammatory response. Here we examined how effectively damage to the lung can be mitigated by administration of drugs initiated at different times after radiation exposure and examined response in adolescent animals for comparison with the young adult animals that we had studied previously. We studied the mitigation efficacy of the isoflavone genistein (50 mg/kg) and the salen-Mn superoxide dismutase-catalase mimetic EUK-207 (8 mg/kg), both of which have been reported to scavenge reactive oxygen species and reduce activity of the NFkB pathway. The drugs were given by subcutaneous injection to 6- to 7-week-old Fisher rats daily starting either immediately or 2 weeks after irradiation with 12 Gy to the whole thorax. The treatment was stopped at 28 weeks post irradiation and the animals were assessed for levels of inflammatory cytokines, activated macrophages, oxidative damage and fibrosis at 48 weeks post irradiation. We demonstrated that both genistein and EUK-207 delayed and suppressed the increased breathing rate associated with pneumonitis. These agents also reduced levels of oxidative damage (50–100%), levels of TGF-β1 expression (75–100%), activated macrophages (20–60%) and fibrosis (60–80%). The adolescent rats developed pneumonitis earlier following irradiation of the lung than did the adult rats leading to greater severe morbidity requiring euthanasia (~37% in adolescents vs. ~10% in young adults) but the extent of the mitigation of the damage was similar or slightly greater.

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Section: Introductionmentioning

confidence: 99%

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

et al. 2012

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“…We studied the combination of whole-lung and whole-torso irradiation to examine how nonlethal multi-organ damage, a possible scenario if there is a radiation accident, might affect lung response. We chose Fischer rats for the study since they are more widely used for long-term studies and have been recommended for long-term radiation studies (13, 25). We gave treatment starting 1 week after irradiation, since many accident victims might not be able to be given treatment immediately after exposure.…”

Section: Introductionmentioning

confidence: 99%

Mitigation of Lung Injury after Accidental Exposure to Radiation

et al. 2011

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There is a serious need to develop effective mitigators against accidental radiation exposures. In radiation accidents, many people may receive nonuniform whole-body or partial-body irradiation. The lung is one of the more radiosensitive organs, demonstrating pneumonitis and fibrosis that are believed to develop at least partially because of radiation-induced chronic inflammation. Here we addressed the crucial questions of how damage to the lung can be mitigated and whether the response is affected by irradiation to the rest of the body. We examined the widely used dietary supplement genistein given at two dietary levels (750 or 3750 mg/kg) to Fischer rats irradiated with 12 Gy to the lung or 8 Gy to the lung + 4 Gy to the whole body excluding the head and tail (whole torso). We found that genistein had promising mitigating effects on oxidative damage, pneumonitis and fibrosis even at late times (36 weeks) when drug treatment was initiated 1 week after irradiation and stopped at 28 weeks postirradiation. The higher dose of genistein showed no greater beneficial effect. Combined lung and whole-torso irradiation caused more lung-related severe morbidity resulting in euthanasia of the animals than lung irradiation alone.

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“…We observed the increase in the 8-oxodG content by low doses of X-ray irradiation. Low doses of irradiation such as 1 to 5 Gy have been reported to increase the 8-oxodG contents in liver DNA of rodents 15,16) and the mutations in mice, 17) while no production of 8-oxodG has been reported at low doses of g-irradiation in some studies. 18,19) Further investigation would be required in order to resolve this confusion.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility of Mouse Splenic Cells to Oxidative DNA Damage by X-Ray Irradiation

Tahara

Kaneko

2004

Biological & Pharmaceutical Bulletin

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Reactive oxygen species (ROS) formed in cells by mitochondrial respiration, phagocytosis, ionizing radiation and chemical oxidizing agents have been shown to be a major cause of oxidative damage to lipids, proteins, DNA, etc. Hydroxyl radicals are suggested to play an important role in the damage caused by ionizing radiation.1-3) Many kinds of oxidative damage are induced in the body by X-ray irradiation. DNA lesions, such as modified bases, abasic sites, and DNA strand breaks, are formed by X-ray irradiation. For example, is formed in DNA by ROS, such as hydroxyl radicals and singlet oxygen, and is recognized as a biomarker of oxidative DNA damage. If 8-oxodG residues are not removed before DNA replication, they cause G-C→T-A transversions. 4)A variety of antioxidant mechanisms in the body protect tissues against damage caused by ROS. 5) In general, susceptibility of mitotic cells to oxidative stress is higher than that of postmitotic cells. If antioxidant defenses are insufficient, ROS could cause damage, including DNA lesions, to cells.Two patterns of cell death, necrosis and apoptosis, are known.6,7) Necrosis results from metabolic collapse in cells, when cells can no longer maintain their homeostasis, while apoptosis is known as programmed cell death, and plays a central role in cell death that occurs during normal development in animals. In this study, the difference in susceptibility of splenic cells as undifferentiated cells and fibroblasts as differentiated cells to X-ray irradiation was examined based on changes in survival rates and 8-oxodG contents. In addition, in order to confirm the process of cell death, we examined whether apoptosis occurs in splenic cells and fibroblasts after X-ray irradiation. MATERIALS AND METHODSAnimals Male BDF1 mice were obtained at 9 or 10 weeks of age from SLC Japan Inc. (Shizuoka, Japan) and housed 4-5 mice per cage under specific-pathogen-free conditions. The animals were fed a commercial laboratory diet, CRF-1 (Oriental Yeast Inc., Tokyo, Japan), and water ad libitum. The animals were maintained at 21Ϯ2°C in a photoperiod-controlled (12 h/d) room.Cell Culture Mice were killed by cervical dislocation under anesthesia and their spleens were quickly isolated and put in phosphate-buffered saline (PBS, pH 7.2). Splenic cells were obtained by leaching the spleens on a #100 gauge wire mesh in a-medium (ICN Biomedicals Inc., Aurora, OH, U.S.A.), and suspended in a-medium supplemented with 30% fetal bovine serum (FBS; Moregate, Melbourne, Australia), 1% deionized bovine serum albumin, 100 mM mercaptethanol, 2 units of human urine erythropoietin (Sigma, St. Louis, MO, U.S.A.) and 10% (v/v) pokeweed-mitogenstimulated murine spleen cell conditioned medium (PWM-SCCM; Stemcell Technologies Inc., Vancouver, BC, Canada). The cell suspension was mixed by pipetting and passed through another mesh. The suspensions (3 ml) containing 5ϫ10 6 splenic cells were incubated at 37°C in 35 mm plastic dishes under a humidified atmosphere of 5% CO 2 and 95% air. Human embryonic fibroblasts, TIG-7...

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Effect of age on the induction of 8-oxo-2′-deoxyguanosine-releasing enzyme in rat liver by γ-ray irradiation

Cited by 16 publications

References 30 publications

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

Mitigation of Radiation-Induced Lung Injury with EUK-207 and Genistein: Effects in Adolescent Rats

Mitigation of Lung Injury after Accidental Exposure to Radiation

Susceptibility of Mouse Splenic Cells to Oxidative DNA Damage by X-Ray Irradiation

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