Recombinant interleukin-2 (IL-2) has demonstrated as an antineoplastic agent in mice and human, but the relatively low response rates observed in clinical trials. Therefore, the present study was undertaken in order to evaluate therapeutic activities of IL-2 for the establishment of therapeutic applications. At the onset of the experiment, normal C3H/HeN mice were injected with $3{\times}10^6$ RD-995 tumor cells, murine ultraviolet radiation-induced fibrosarcoma, subcutaneously. Beginning on day 25, experimental groups were treated with a 5-day course of IL-2 (subcutaneous injection of 30,000 IU every 12 hours for 5 days). The result of this experiment revealed that RD-995 tumor grew progressively in control mice. Subcutaneous IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 therapy decreased tumor growth until day 23, then the tumor grew progressively. No significant difference in the survival of IL-2 treated mice were observed compared with the control mice.
Despite increased evidence of bio-activity following far-infrared (FIR) radiation, susceptibility of cell signaling to FIR radiation-induced homeostasis is poorly understood. To observe the effects of FIR radiation, FIR-radiated materials-coated fabric was put on experimental rats or applied to L6 cells, and microarray analysis, quantitative real-time polymerase chain reaction, and wound healing assays were performed. Microarray analysis revealed that messenger RNA expressions of rat muscle were stimulated by FIR radiation in a dose-dependent manner in amount of 10% and 30% materials-coated. In 30% group, 1,473 differentially expressed genes were identified (fold change [FC] > 1.5), and 218 genes were significantly regulated (FC > 1.5 and p < 0.05). Microarray analysis showed that extracellular matrix (ECM)-receptor interaction, focal adhesion, and cell migration-related pathways were significantly stimulated in rat muscle. ECM and platelet-derived growth factor (PDGF)-mediated cell migration-related genes were increased. And, results showed that the relative gene expression of actin beta was increased. FIR radiation also stimulated actin subunit and actin-related genes. We observed that wound healing was certainly promoted by FIR radiation over 48 h in L6 cells. Therefore, we suggest that FIR radiation can penetrate the body and stimulate PDGF-mediated cell migration through ECM-integrin signaling in rats.
The effects of UV-B radiation on the seedling growth, carbohydrate metabolism and antioxidants activities of rice (Oryza sativa L.) were investigated under environmentally controlled chamber. Supplementary UVB radiation reduced dry matter as well as leaf area, therefore, relative growth rates (RGR) of seedlings were decreased by up to half compared to control. Photosynthetic products such as soluble sugars and starch were rapidly and significantly reduced by within 1 day of enhanced UV-B radiation due to the inhibition and degradation of photosynthetic processes and thylakoid membrane integrity. In our study, nonstructural carbohydrate levels were proved to be a main indicator on UV-Binduced stress. The behavior of SOD, CAT, APX and POD activities was monitored in the leaves of rice seedlings subjected to UV-B radiation. Under UV-B treatments, SOD activity was initially increased, whereas CAT and POD activities were slowly and slightly increased. However, APX activity showed no presumable results with an increase of UV-B dose. In leaves of rice seedlings, supplementary UV-B radiation caused an increase in free putrescine and spermidine, however spermine remained unaltered, although 24-hrs UV-B treatment slightly increased. This result presumes that an excess UV-B dose may induce ethylene biosynthesis (senescence) rather than polyamine biosynthesis (defense).
Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation. Methods: We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis. Results: PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings. Conclusion: The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.
Lee Hyung Sik;Park Hong Kyu;Hur Won Joo;Seo Su Yeong;Lee Sang Hwa;Jung Min Ho;Park Heon Joo;Song Chang Won
Radiation Oncology Journal
/
v.16
no.2
/
pp.91-98
/
1998
Purpose : The relationship between environmental PH on the radiation induced-apoptosis in SCK mammary adenocarcinoma cells and cell cycle dependence was investigated. Material and Methods : Mammary adenocarcinoma cells of A/J mice(SCK cells) in exponential growth phase were irradiated with a $l37^Cs$ irradiator at room temperature. The cells were irradiated 1 hour after the media was replaced with fresh media at a different pHs. After incubation at $37^{\circ}C$ for 0-48 h, the extent of apoptosis was determined using agarose gel electrophoresis and flow cytometry. The progression of cells through the cell cycle after irradiation in different pHs was also determined with flow cytometry. Bssults : The induction of apoptosis by irradiation in pH 6.6 medium was markedly less than that in pH 7.5 medium. When the cells were irradiated and maintained in pH 7.5 medium, the percentage of cells in $G_2/M$ phase rapidly increased to about $70\%$ at 12 h after an exposure to 120y and returned to control level by 36 h. The percentage of cells in G1 phase decreased as the percentage of cells in $G_2/M$ increased. On the other hand, in pH 6.6 medium the percentage of cells in G2/M phases gradually increased to about $45\%$ at 24 h after 12Gy irradiation and then slowly recessed and consequently, as much as $30-35\%$ of the cells were still in the Ga/M phase 48 h after irradiation. The percentage of cells in G1 phase then increased as the Ga/M arrest began to recede. The radiation-induced Ga/M arrest in PH 0.0 medium lasted markedly longer than that in pH 7.5 medium. Conclusion : Radiation-induced apoptosis in SCK tumor cells are reversely suppressed in an acidic environment. Radiation-induced Ga/M arrest is prolonged in an acidic environment indicating that the suppression of radiation-induced apoptosis and prolongation of radiation-induced Ga/M arrest in an acidic environment are related.
Background: The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Materials and Methods: Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose ($D_0$), quasi-threshold dose ($D_q$) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM). Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. Results: The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Conclusions: Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA-MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.
To investigate alleviation effects of salt stress by low dose gamma-irradiation on seedling growth of rice (Oryza shrive L), in plants of two rice cultivars (Ilpumbyeo and Gancheokbyeo), seeds were irradiated with the different doses $(0{\sim}32\;Gy)$ of gamma-ray by irradiator ($^{60}Co$, ca.150 TBq of capacity, AECL). The salt stress caused a remarkable decrease of seedling growth, particularly for dry weight. In addition, relative growth rate was decreased over 50% by the salt stress. However, the salt stress-induced inhibition of growth was alleviated by gamma-irradiation. Especially, the relative growth rate of shoot showed the reduction effect over 30% at 4 Gy-irradiated groups as compared with that of control. Also, electrolyte leakage and relative water content were damaged, respectively 4 times and 30% by the salt stress but the damages were alleviated by the gamma-irradiation. These alleviation effects were observed similarly in both the cultivars tested. These results suggest that the low dose gamma-irradiation may have a better protection or the salt stress.
Deinococcus radiodurans is extremely resistant to various genotoxic conditions and chemicals. In this study, we characterized the effect of a sublethal concentration (100 ${\mu}M$) of cadmium (Cd) on D. radiodurans using a whole-genome DNA microarray. Time-course global gene expression profiling showed that 1,505 genes out of 3,116 total ORFs were differentially expressed more than 2-fold in response to Cd treatment for at least one timepoint. The majority of the upregulated genes are related to iron uptake, cysteine biosynthesis, protein disulfide stress, and various types of DNA repair systems. The enhanced upregulation of genes involved in cysteine biosynthesis and disulfide stress indicate that Cd has a high affinity for sulfur compounds. Provocation of iron deficiency and growth resumption of Cd-treated cells by iron supplementation also indicates that CdS forms in iron-sulfur-containing proteins such as the [Fe-S] cluster. Induction of base excision, mismatch, and recombinational repair systems indicates that various types of DNA damage, especially base excision, were enhanced by Cd. Exposure to sublethal Cd stress reduces the growth rate, and many of the downregulated genes are related to cell growth, including biosynthesis of cell membrane, translation, and transcription. The differential expression of 52 regulatory genes suggests a dynamic operation of complex regulatory networks by Cd-induced stress. These results demonstrate the effect of Cd exposure on D. radiodurans and how the related genes are expressed by this stress.
It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.
Radiation at very low doses frequently has a stimulating or hermetic effect on growth of organism. Effects of growth and survival rate on various dose of gamma irradiation in the farm culture of juvenile abalone (Haliotis discus hannai) were determined in Hallim (Jeju) from February 2004 to January 2005. The initial shell length of abalone juveniles in this study was average $3.45{\pm}0.4cm$. A change of growth after irradiation $(0{\sim}20Gy)$ was observed for 48 weeks. The highest growth rate was observed in 4 Gy-irradiated group and the lowest growth rate was observed in 20 Gy-irradiated group. The additional research about biochemical changes on juvenile abalone after irradiation should be accomplished. Continuous study for gamma radiation-induced hormesis on growth and metabolism of juvenile abalone will further induce the creation of value in ocean industry.
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