In Vivo Nitric Oxide Production and iNOS Expression in X-Ray Irradiated Mouse Skin

Chi, Cuiping; Ozawa, Toshihiko; Anzai, Kazunori

doi:10.1248/bpb.29.348

Cited by 12 publications

(3 citation statements)

References 37 publications

(34 reference statements)

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“…22) We consider that the initial appearance of nitric oxide after irradiation was generated by existing NOS, without synthesis of NOS protein. There are three known isoforms of NOS; eNOS (endothelial NOS), iNOS (inducible NOS) and nNOS (neuronal NOS).…”

Section: Discussionmentioning

confidence: 99%

The Role of Nitric Oxide in Radiation Damage

Ohta

Matsuda

Gunji

et al. 2007

Biological & Pharmaceutical Bulletin

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Free radicals, such as hydrogen and hydroxyl radicals, are produced in aqueous solution after X-irradiation. 1) They react with body tissues and generate lipid peroxidation, DNA lesions and enzyme inactivation, all of which are mediators of radiation damage. [2][3][4][5] Nitric oxide is another free radical induced by irradiation.6,7) Nitric oxide induces vasorelaxation and inhibition of platelet aggregation and thus, can improve hypertension or prevent thrombosis. In contrast, nitric oxide can also have cytotoxic effects. Administration of Nomeganitroarginine methyl ester (L-NAME), which is the nitric oxide synthase (NOS) inhibitor, can prevent enteritis after irradiation. 8) This suggests that nitric oxide may be related to irradiation-induced injury. However, early endothelial injury following radiation exposure causes kidney damage with hypertension, capillary thrombosis and death from renal failure. Hypertension and thrombosis could be caused by a deficit of NOS and indeed, the administration of a nitric oxide emission reagent increases survival time after irradiation. 9) Therefore, it is unclear whether nitric oxide affects protection or injury after irradiation, and its relationship to radiation damage has not been examined.Our continuing research of the radioprotective action of sulfur compounds has been reported over a number of years. [10][11][12][13][14][15] Of the sulfur compounds we have studied, S-2-aminoethylisothiourea 2HBr (AET) 12) is a representative drug in the research of experimental radiation damage protectors. Although AET has an effect on the NOS inhibitor, [16][17][18][19] the relationship between radiation damage protection and inhibition of NOS has not been clarified. This study investigated the role of nitric acid in relation to radiation damage, by examining changes in mouse serum nitrate concentrations after irradiation. The mechanisms of radiation damage protection mediated by AET were also clarified. MATERIALS AND METHODS Laboratory AnimalsFive-week-old male ICR strain mice (Charles River Japan, Inc., Yokohama, Japan) were given nutritional chow (MF; Oriental Yeast Co., Ltd., Tokyo, Japan) and water ad libitum. Mice weighing 32Ϯ3 g (about six-week-old) were used throughout the studies.Irradiation Method Irradiation experiments were carried out by a soft X-ray irradiator (Softex M-100WE; Softex Co., Ltd., Tokyo, Japan). Mice were placed in a circular polystyrene cage (diameter: 150 mm, depth: 23 mm) and covered with a net (mesh: 10 mm), then put on a revolving stage at a distance 400 mm below the source. The animals were wholebody irradiated from the dorsum, using various doses (19.6-31.5 Gy) at 70 kVp, 10 mA, a 10 mm acrylic filter and 0.8 Gy/min. Dose rate of the experiments was determined by a Victoreen model 500 dosimeter, using a model 500-6 A type probe.The irradiation groups were irradiated at doses described in the Results. The non-irradiation group served as a control.Methods for Coordination and Injection of the Drug Lipopolysaccharide E. coli (LPS; Difco Laboratories, D...

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Section: Discussionmentioning

confidence: 99%

The Role of Nitric Oxide in Radiation Damage

Ohta

Matsuda

Gunji

et al. 2007

Biological & Pharmaceutical Bulletin

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“…The expression of chromatin assembly factor 1 (CAF-1) and proliferating cell nuclear antigen (PCNA) is dramatically induced as a result of DNA damage by the radiomimetic drug bleocin (a bleomycin compound) or by IR [ 11 ]. The expression of inducible nitric oxide synthase (iNOS) in X-ray irradiated mouse skin at both the mRNA and protein levels was recently published [ 12 ]. The expression and activation of MMP -2, -3, -9, -14 are induced in rat colon after abdominal X-irradiation [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Gene Expression in Normal and Cancer Cells Exposed toγ-Radiation

Chaudhry

2008

Journal of Biomedicine and Biotechnology

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The expression of many genes is modulated after exposure to ionizing radiation. Identification of specific genes may allow the determination of pathways important in radiation responses. We previously identified modulation of the expression of several genes in response to ionizing radiation treatment. In the present study, we monitored the expression of RGS1, CC3, THBS1, vWF, MADH7, and a novel gene encoding a secreted protein in irradiated Jurkat, TK6, HeLa, and HFL1 cells. The RGS1 is involved in G-protein signaling pathway, CC3 belongs to the complement system, THBS1 is a component of the extracellular matrix, vWF takes part in blood coagulation, and MADH7 is a member of the TGF-β signal transduction pathway. Our objective was to find similarities and differences in the expression of these genes in ionizing radiation-exposed diverse cell types. RGS1 was downregulated in Jurkat cells but was upregulated in TK6 and HFL1 cells. The expression of CC3 was repressed in Jurkat and HFL1 cells but was induced in TK6 and HeLa cells. THBS1 was downregulated in irradiated TK6 and HFL1 cells. vWF was induced in radiation-exposed HeLa cells, but its expression was downregulated in Jurkat cells. The expression of MADH7 was induced in all the cell types examined. These results indicate cell specific modulation of gene expression and suggest the involvement of different pathways in cellular response to radiation treatment in different cells.

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“…Multiple lines of evidence suggest that NO is a modulator of radiation response. First, generation of NO has been reported in leukocytes and in skin cells following WBI [15,16]. Second, soluble factors released from irradiated lymphocytes initiate a signaling cascade in unirradiated lymphocytes resulting in immunomodulation [24].…”

Section: Discussionmentioning

confidence: 99%

Differential activation of NF-κB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity

Sharma

Sandur

Rashmi

et al. 2010

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Lymphocytes are more sensitive to radiation in vivo than in vitro. However, the mechanism of this differential response is poorly understood. In the present study, it was found that the lipid peroxidation and cell death were significantly higher in lymphocytes following whole body irradiation (WBI) as compared to lymphocytes exposed to radiation in vitro. EL-4 cells transplanted in mice were also more sensitive to radiation than EL-4 cells irradiated in vitro. DNA repair, as assessed by comet assay, was significantly faster in lymphocytes exposed to 4 Gy radiation in vitro as compared to that in lymphocytes obtained from whole body irradiated mice exposed to the same dose of radiation. This was associated with increased NF-κB activation in response to genotoxic stress and lesser activation of caspase in lymphocytes in vitro compared to in vivo. To explain the differential radiosensitivity, we postulated a role of nitric oxide, an extrinsic diffusible mediator of radiosensitivity that has also been implicated in DNA repair inhibition. Nitric oxide levels were significantly elevated in the plasma of whole body irradiated mice but not in the supernatant of cells irradiated in vitro. Addition of sodium nitroprusside (SNP), a nitric oxide donor to cells irradiated in vitro inhibited the repair of DNA damage and enhanced apoptosis (increased Bax to Bcl-2 ratio). Administration of L-NAME, a nitric oxide synthase inhibitor, to mice significantly protected lymphocytes against WBI-induced DNA damage and inhibited in vivo radiation-induced production of nitric oxide. These results confirm that the observed differential radiosensitivity of lymphocytes was due to slow repair of DNA due to nitric oxide production in vivo.

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In Vivo Nitric Oxide Production and iNOS Expression in X-Ray Irradiated Mouse Skin

Cited by 12 publications

References 37 publications

The Role of Nitric Oxide in Radiation Damage

The Role of Nitric Oxide in Radiation Damage

Analysis of Gene Expression in Normal and Cancer Cells Exposed toγ-Radiation

Differential activation of NF-κB and nitric oxide in lymphocytes regulates in vitro and in vivo radiosensitivity

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