Seong Soon Jang

Melatonin exerts differential actions on X-ray radiation-induced apoptosis in normal mice splenocytes and Jurkat leukemia cells

Abstract:  The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation‐induced apoptosis by melatonin and the expression of apoptosis‐associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X‐ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation‐only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was detected by TUNEL assay at 8 hr after irradiation. At this time, the apoptotic index of irradiation‐only and melatonin pretreatment groups were 35.6% and 20.7%, respectively. This reduced apoptosis by melatonin was associated with the increase of Bcl‐2 expression and a reduction of Bax/Bcl‐2 ratio through a relative decrease of p53 mRNA and protein. In the Jurkat cells treated with a combination of melatonin and radiation, both Annexin V‐FITC(+)/PI(−) and Annexin V‐FITC(+) cells were increased at 48 hr after irradiation when compared with irradiation‐only or melatonin alone. The expressions of p53 between groups were well correlated with the results of Annexin V binding. The irradiation or melatonin did not influence the JNK1 expression in Jurkat cells. The present results suggest that melatonin enhances radiation‐induced apoptosis in Jurkat leukemia cells, while reducing radiation‐induced apoptosis in normal mice splenocytes. These differential effects on radiation‐induced apoptosis by melatonin might involve the regulation of p53 expression.

Melatonin reduces X-ray radiation-induced lung injury in mice by modulating oxidative stress and cytokine expression

Abstract Purpose: The modification of radiation-induced lung injuries by melatonin was studied by measuring changes in oxidative stress, cytokine expression and histopathology in the lung tissue of mice following irradiation. Materials and methods: The thoraces of C57BL/6 mice were exposed to a single X-ray radiation dose of 12 Gy with or without 200 mg/kg of melatonin pretreatment. The level and localization of transforming growth factor (TGF)-β1 protein were measured using an enzyme-linked immunosorbent assay (ELISA) method and immunohistochemical staining, respectively. Real-time quantitative polymerase chain reaction (PCR) was established to evaluate the relative mRNA expression levels of TGF-β1, tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6. Results: Malondialdehyde (MDA) levels increased after irradiation and then significantly reduced (1.9-fold) under melatonin treatment. Changes in superoxide dismutase (SOD) and catalase activities, as well as glutathione (GSH) levels, after irradiation were significantly reduced by melatonin, including a notable 5.4-fold difference in catalase activity. We observed increased expression of TGF-β1 and TNF-α after irradiation and a significant reduction in the elevation of their expression by melatonin treatment. Furthermore, irradiation-induced histopathologic alterations were obviously abated in the melatonin-pretreated mice. Conclusions: The present results suggest that melatonin reduces radiation-induced lung injury via a significant reduction of oxidative stress and of the production of cytokines, such as TGF-β1 and TNF-α, the production of which increased following lung irradiation.

Fenofibrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells

Purpose The fibrates are ligands for peroxisome proliferator-activated receptor (PPAR) α and used clinically as hypolipidemic drugs. The fibrates are known to cause peroxisome proliferation, enhance superoxide dismutase (SOD) expression and catalase activity. The antioxidant actions of the fibrates may modify radiation sensitivity. Here, we investigated the change of the radiation sensitivity in two cervix cancer cell lines in combination with fenofibrate (FF). Materials and Methods Activity and protein expression of SOD were measured according to the concentration of FF. The mRNA expressions were measured by using real time reverse-transcription polymerase chain reaction. Combined cytotoxic effect of FF and radiation was measured by using clonogenic assay. Results In HeLa cells total SOD activity was increased with increasing FF doses up to 30 µM. In the other hand, the catalase activity was increased a little. As with activity the protein expression of SOD1 and SOD2 was increased with increasing doses of FF. The mRNAs of SOD1, SOD2, PPARα and PPARγ were increased with increasing doses of FF. The reactive oxygen species (ROS) produced by radiation was decreased by preincubation with FF. The surviving fractions (SF) by combining FF and radiation was higher than those of radiation alone. In Me180 cells SOD and catalase activity were not increased with FF. Also, the mRNAs of SOD1, SOD2, and PPARα were not increased with FF. However, the mRNA of PPARγ was increased with FF. Conclusion FF can reduce radiation sensitivity by ROS scavenging via SOD induction in HeLa. SOD induction by FF is related with PPARα.

Modulation of radiation-induced alterations in oxidative stress and cytokine expression in lung tissue by Panax ginseng extract.

We investigated the modulating effect of Panax ginseng extract (PGE) on radiation‐induced lung injury (RILI) by measuring early changes in oxidative stress levels, cytokine expression, and the histopathology of mouse lung tissue treated with high dose of X‐ray radiation. The mice were pretreated with 25, 50, and 100‐mg/kg doses of PGE orally for four consecutive days, and their thoraces were then exposed to 15‐Gy X‐ray radiation 1 h after the last administration of PGE on day 4. The pretreatments with 50 and 100 mg/kg PGE led to significant reductions in the elevation of lipid peroxidation levels at 2 and 10 days, respectively, after irradiation. The mice pretreated with PGE exhibited dose‐dependent reductions in the irradiation‐induced production of tumor necrosis factor α and transforming growth factor β1 cytokines 10 days after irradiation, with these reductions nearly reaching the control levels after the 100‐mg/kg dose. Furthermore, together with providing significant protection against reductions in catalase activity and glutathione content, pretreatment with 100 mg/kg PGE resulted in a marked attenuation of the severity of inflammatory changes in lung tissue 10 days after irradiation. A high pretreatment dose of PGE may be a useful pharmacological approach for protection against RILI. Copyright

Usefulness of target delineation based on the two extreme phases of a four-dimensional computed tomography scan in stereotactic body radiation therapy for lung cancer.

An evaluation of the usefulness of target delineation based only on the two extreme phases of a four‐dimensional computed tomography (4D CT) scan in lung stereotactic body radiation therapy (SBRT).

Three-dimensional conformal reirradiation for locoregionally recurrent lung cancer previously treated with radiation therapy.

To evaluate the efficacy and toxicity of reirradiation using three‐dimensional conformal radiotherapy (3D‐CRT) in symptomatic patients with locoregionally recurrent lung cancer.