• Radiation Oncology Journal
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• v.14 no.4
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• pp.255-264
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• 1996

Purpose : Paclitaxel is a chemotherapeutic agent with potent microtubule stabilizing activity that arrests cell cycle in $G_2$-M Because $G_2$-M is the most radiosensitive Phase of the cell cycle, paclitaxel has potential as a cell cycle- specific radiosensitizer. This study was designed to investigate the ability of paclitaxel to increase the radiotoxicity in normal small bowel mucosa of the rat. materials and Methods : A sigle intraperitoneal infusion of paclitaxel (10mg/kg), and a single irradiation(8 Gy, x-ray) to the whole abdomen and combination of radiation(8 Gr, x-ray) 24 hours after paclitaxel infusion in the rats were done. The changes of jejunal mucosa, and kinetics of mitotic arrest and apoptosis in the jejunal crypt were defined at 6 hours - 5 days after each treatment histologically. Results : Paclitaxel blocked jejunal crypt cell in mitosis and induced minmal apoptosis. Mitotic arrest by paclitaxel was peaked at 6 hours after infusion and returned to normal by 24 hours. Radiation induced apoptosis and peaked at 6 hours and returned to normal by 24 hours. Combination of paclitaxel and radiation blocked crypt cell in mitosis at 3 days and induced apoptosis slightly at 6 hours and 24 hours and returned to normal by 3 days. The incidence of apoptosis in combined group at 6 hours was slightly higher than normal control but significantly lower than radiation alone group. The major changes of jejunal mucosa were nuclear vesicle and atypia which were appeared at 6 hours - 3 days and returned to normal by 5 days The degree of the mucosal changes are not different in 3 groups except for absence of inflmmatory reaction in radiation group. Conclusion : Mitotic arrest by paclitaxel was peaked at 6 hours and returned to normal by 24 hours and paclitaxel induced minimal apoptosis. Radiation induced apoptosis, peaked at 6 hours and returned to normal by 24 hours. Radiation-induced apoptosis was less in combined group which suggested that paclitaxel have a radioprotective effect when radiation was given 24 hours after paclitaxel infusion.

• The Journal of Korean Society for Radiation Therapy
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• v.12 no.1
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• pp.166-173
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• 2000

Angiopoietin-1(Ang-1) is a vasculogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. We examined the effect of angiopoietin-1(Ang-1) on radiation-induced apoptosis in human umbilical vein endothelial cells(HUVECS) and receptor/second messenger signal transduction pathway for Ang-1's effect on HUVECs. The percent of apoptotic cells under control condition(0Gy) was $8.2\%$. Irradiation induced apoptosis was increased in a dose(1, 5, 10, and 15Gy)- and time 12, 24, 48 and 72hr)-dependent manner. The percent of apoptotic cells was approximately $34.9\%$ after 15 Gy of irradiation. Under these conditions, pretreatment with Ang-1's (50, 100, 200, and 400 ng/ml) inhibited irradiation-induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner. Two hundred ng/ml of Ang-1 inhibited approximately $55-60\%$ of the apoptotic events that occurred in the 10 Gy-irradiated cells. Pre-treatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang-1's antiapoptotic effects. Phosphatidylinositol 3'-kinase (P13-kinase) specific inhibitor, wortmanin and LY294002, blocked the Ang-1-induced antiapoptotic effect. Ang-1 promotes the survival of endothelial cells in irradiation-induced apoptosis through Tie2 receptor binding and P13-kinase activation. Pretreatment of Ang-1 could be beneficial in maintaining normal endothelial cell integrity during irradiation therapy.

• Radiation Oncology Journal
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• v.18 no.3
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• pp.205-213
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• 2000

Purpose : To determine the role of cytokines in the apoptosis of rat's liver following irradiation. Materials and Methods : Sprague-Dawley rats were irradiated to entire body with a single dose of 8 Gy. The rats were divided Into 5 groups according to the sacrlfice day after irradiation. The liver and blood after 1, 3, 5, 7, and 14 days irradiation were sampled for evaluation of mechanism of apoptosis and role of cytokine in relation to radiation-induced tissue damage. The study was composed of microscopic evaluation of liver tissue, in situ detection method for apoptosis, immunohistochemical stain of IL-1, IL-4, IL-6 and TNF, bioassay and radioimmunoassay of IL-6 in liver tissue and blood. Results : Radiation-induced liver damage was noted from first day of radiation, and most severe parenchymal damage associated with infiltration of chronic inflammatory cells was seen in the groups of 5 days after radiation. A number of apoptosis were observed 1 day after radiation on both light microscope and in situ method. Afterwards, the number of apoptosis was gradually diminished. On immunohistochemical study, IL-1 and TNF were expressed 1, 3 days after radiation, but not expressed after that. IL-4 was not expressed in the entire groups. IL-6 was expressed with strong positivity in 1, 3 days after radiation. Bioassay and RIA of IL-6 in liver tissue and blood showed the highest value in 1 day after radiation, and the value is diminished after then. Conclusion. Apoptosis seemed to be the important mechanism of radiation-induced liver damage, and is possibly induced by the release of cytokines, such as IL-1, IL-6, TNF in view the simultaneously increased appearance of pooptosis and cytokines.

• Natural Product Sciences
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• v.19 no.2
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• pp.127-136
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• 2013

Ionizing radiation, including that evoked by gamma (${\gamma}$)-rays, induces oxidative stress through the generation of reactive oxygen species, resulting in apoptosis, or programmed cell death. This study aimed to elucidate the radioprotective effects of hyperoside (quercetin-3-O-galactoside) against ${\gamma}$-ray radiation-induced apoptosis in Chinese hamster lung fibroblasts, V79-4 and demonstrated that the compound reduced levels of intracellular reactive oxygen species in ${\gamma}$-ray-irradiated cells. Hyperoside also protected irradiated cells against DNA damage (evidenced by pronounced DNA tails and elevated phospho-histone H2AX and 8-oxoguanine content) and membrane lipid peroxidation. Furthermore, hyperoside prevented the ${\gamma}$-ray-provoked reduction in cell viability via the inhibition of apoptosis through the increased levels of Bcl-2, the decreased levels of Bax and cytosolic cytochrome c, and the decrease of the active caspase 9 and caspase 3 expression. Taken together, these results suggest that hyperoside defend cells against ${\gamma}$-ray radiation-induced apoptosis by inhibiting oxidative stress.

• The Journal of Korean Society for Radiation Therapy
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• v.19 no.2
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• pp.83-90
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• 2007

Purpose: In this study, it was investigated whether commercially produced beer is able to prevent a lymphocyte from radiation induced apoptosis. Materials and Methods: Whole blood samples were acquired from 5 healthy volunteers (male, 26$\sim$38 years old) and the lymphocyte were isolated by density gradient centrifugation. Radiation induced apoptosis of the lymphocyte were investigated by 0.5 Gy, 1.0 Gy, 2.0 Gy, 3.0 Gy to 5.0 Gy irradiation. In some experiments, the donor drunk beer and then blood samples were collected. In other experiments, melatonin or glycine betain was added to lymphocyte culture medium. Treated or untreated lymphocytes were cultured for 60 hours and radiation induced apoptosis of the lymphocyte was analyzed by annexin-V staining through flow cytometery. Results: Relative radiation induced apoptosis ratio of the untreated lymphocytes is 1.22$\pm$1.1, 1.22$\pm$1.1, 1.38$\pm$1.0, 1.47$\pm$1.1, 1.50$\pm$1.2 by radiation dose of 0.5 Gy, 1.0 Gy, 2.0 Gy, 3.0 Gy and 5.0 Gy respectively. Relative radiation induced apoptosis ratio of lymphocytes is isolated from beer drunken donors is 0.97$\pm$1.0, 0.99$\pm$1.0, 1.11$\pm$0.9, 1.29$\pm$1.1, 1.15$\pm$1.1 by radiation doses respectively which are reduced 21.5% compared with untreated lymphocyte. Relative radiation induced apoptosis ratio of the lymphocytes is isolated from non-alcohol beer drunken donors is 1.22$\pm$1.1, 1.17$\pm$1.1, 1.13$\pm$1.3, 1.38$\pm$1.2, 1.32$\pm$1.1 by radiation dose of 0.5 Gy, 1.0 Gy, 2.0 Gy, 3.0 Gy and 5.0 Gy respectively which are reduced 10.8% compared with the untreated lymphocyte. Conclusion: As a result, it is suggested that beer may protect the lymphocyte from radiation damage and inhibit apoptosis.

• Radiation Oncology Journal
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• v.20 no.3
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• pp.246-252
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• 2002

Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.312-319
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• 2016

Human skin cells undergo pathophysiological processes via generation of reactive oxygen species (ROS) upon excessive exposure to ultraviolet B (UVB) radiation. This study investigated the ability of hesperidin ($C_{28}H_{34}O_{15}$) to prevent apoptosis due to oxidative stress generated through UVB-induced ROS. Hesperidin significantly scavenged ROS generated by UVB radiation, attenuated the oxidation of cellular macromolecules, established mitochondrial membrane polarization, and prevented the release of cytochrome c into the cytosol. Hesperidin downregulated expression of caspase-9, caspase-3, and Bcl-2-associated X protein, and upregulated expression of B-cell lymphoma 2. Hesperidin absorbed wavelengths of light within the UVB range. In summary, hesperidin shielded human keratinocytes from UVB radiation-induced damage and apoptosis via its antioxidant and UVB absorption properties.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.159-168
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• 2017

Background: Radiotherapy is one of the most important modalities in cancer treatment; however, normal tissue damage is a serious concern. Drug development for the protection or reduction of normal tissue damage is therefore a clinical issue. Herein, we evaluated the protective properties of Panax ginseng Meyer and its corresponding mechanisms. Methods: C56BL/6 mice were orally pretreated with P. ginseng water extract (PGE; 25 mg/kg, 50 mg/kg, or 100 mg/kg) or intraperitoneally injected melatonin (20 mg/kg) for 4 d consecutively, then exposed to 15-Gy X-ray radiation 1 h after the last administration. After 10 d of irradiation, the biological properties of hematoxicity, fat accumulation, histopathology, oxidative stress, antioxidant activity, pro-inflammatory cytokines, and apoptosis signals were examined in the hepatic tissue. Results: The irradiation markedly induced myelosuppression as determined by hematological analysis of the peripheral blood. Steatohepatitis was induced by X-ray irradiations, whereas pretreatment with PGE significantly attenuated it. Oxidative stress was drastically increased, whereas antioxidant components were depleted by irradiation. Irradiation also notably increased serum liver enzymes and hepatic protein levels of pro-inflammatory cytokines. Those alterations were markedly normalized by pretreatment with PGE. The degree of irradiation-induced hepatic tissue apoptosis was also attenuated by pretreatment with PGE, which was evidenced by a terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick-end labeling assay, western blotting, and gene expressions analysis, particularly of apoptotic molecules. Conclusion: We suggest that PGE could be applicable for use against radiation-induced liver injury, and its corresponding mechanisms involve the modulation of oxidative stress, inflammatory reactions, and apoptosis.

• Korean Journal of Veterinary Pathology
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• v.2 no.1
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• pp.37-46
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• 1998

It has been known that $\gamma$-irradiation usually induces cell death in regenerating stem cell in normal tissues like skin, intestine and hematopoietic organ. The experiment were carried out to evaluate the early response of radiation injury in radiosensitive and intermediate radiosensitive tissues in feeding and starving rats with the doses of 3.5 and 7.0 Gy. The results of the study showed that the histological phenomenon was apoptosis in the doses of the radiation as the early response of tissue injury. Apoptosis were showed organ-specific and cellular specific responses suggesting that the selection of apoptosis be exactly focused on highly renewal organs and cells. It was interesting that the rats starved for 72 hours prior to irradiation induced less apoptosis in liver than fed rats. As for cellular responses it appeared that apoptotic cells were mostly distributed in ductal or periportal cells in liver of feeding rats unlikely in liver of Starving rots which showed no difference in zonal distribution. In salivary gland apoptotic cells in fed rats were highly induced in intercalating and ductal cell population than in acinar cell population although unlikely in starved rats. This study showed the value of apoptosis using the detection system of TUNEL for evaluating cellular damage after radiation injury and the diminished effect of starvation on cell damage after ionizing irradiation.

• The Korean Journal of Nuclear Medicine
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• v.34 no.2
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• pp.144-153
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• 2000

Purpose: The purpose of this study was to evaluate the relationship between radiation-induced activation of DNA repair genes and radiation induced apoptosis in A431 cell line. Materials and Methods: Five and 25 Gys of gamma radiation were given to A431 cells by a Cs-137 cell irradiator. Apoptosis was evaluated by flow cytometry using annexin V-fluorescein isothiocyanate and propidium iodide staining. The expression of DNA repair genes was evaluated by both Northern and Western blot analyses. Results: The number of apoptotic cells increased with the increased radiation dose. It increased most significantly at 12 hours after irradiation. Expression of p53, p21, and hRAD50 reached the highest level at 12 hours after 5 Gy irradiation. In response to 25 Gy irradiation, hRAD50 and p21 were expressed maximally at 12 hours, but p53 and GADD45 genes showed the highest expression level after 12 hours. Conclusion: Induction of apoptosis and DNA repair by ionizing radiation were closely correlated. The peak time of inducing apoptosis and DNA repair was 12 hours in this study model. hRAD50, a recently discovered DNA repair gene, was also associated with radiation-induced apoptosis.