C37. Supressed effect of glyceryl trinitrate on tumor

Poster abstracts / Nitric Oxide 17 (2007) S20–S29 C36. Can nitric oxide be used as a predictor of radiation response? B. Vesper, M.B. Altman, K.M. Elseth, J.C. Roeske, G.K. Haines, K.W. Altman, B.G. Bentz, J.A. Radosevich University of Illinois at Chicago, 801 S. Paulina St., Center for Molecular Biology of Oral Diseases, Chicago, USA Objectives: Intensity-modulated radiation therapy (IMRT) is commonly used to treat tumors; however, there are currently no predictors to determine how patients will respond to treatment. Recent work has shown that tumor cells over-express nitric oxide (NO) and its corresponding protective mechanism, Glutathione-S-Transferase (GST-pi), thus allowing tumors to grow more aggressively and be more resistant to treatment methods. Using a custom-built IMRT phantom, we tested the potential protective effects of NO on squamous cell carcinoma (SCC) cell lines. Methods: Three head and neck SCC cell lines (SCC040, SCC056, and SCC116) and one normal cell line (WI-38) were adaptively grown in increasing concentrations of DETA NONOate. Each NO-adapted cell line, along with its corresponding parent (non-adapted) cell line, were exposed to radiation (1-28 Gy). Cell viability/proliferation was measured using the DPA assay. Results: All three tumor cell lines showed increased radioresistance upon exposure to NO, relative to the parent line, while the normal cells did not show a measurable difference between the parent and NO-adapted cell line. Conclusions: These results suggest that the SCC cell lines may express a comparatively high level of NO/GST-pi relative to normal cells. Future work will determine the relative amounts of NO/ GST-pi expression for the parent and adapted cell lines, in order to correlate expression levels with the radiation results obtained in this study. Such correlation would suggest that NO expression may be useful as a predictor for radiation treatment outcome. doi:10.1016/j.niox.2007.09.081

C37. Supressed effect of glyceryl trinitrate on tumor T. Yaping, Y. Zhang, J. Dong, D. Wang Department of Clinical Biochemistry, Chinese PLA General Hospital, 28 Fu Xing Road, Beijing, PR China Glyceryl trinitrate (GTN) had been used in clinic therapy for more than a century, e.g., for treating congestive heart failure and vasodilation. Many studies done on the metabolic mechanism of GTN showed that it would deplete reduced glutathione (GSH) and produce nitric oxide (NO) and nitrite. In recent years, many studies showed that NO and nitrite could modulate proliferation of tumor cells. The present study was designed to determine whether GTN had potential effect on tumor therapy. In the study, we examined the regulatory mechanisms and effects of GTN on tumor by using cell culture and animal model. For this purpose, the metabolism of GTN in vitro and the effects of GTN on Bcl-2 protein,

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cell cycle, apoptosis index and GSH of the cultured Hela cells were observed. In order to explore the effects of GTN on the growth of tumor in the inoculated animals, GTN was given through gastrointestinal tract, and the growth of sarcoma 180 and the change of blood biochemistry value of the experiment mice were observed. We had demonstrated that GTN possesses the characteristics of inhibiting the growth of tumor cells by depleting GSH, modulating cell cycles, down-regulating expression of Bcl-2 and prompting apoptosis. The inhibitory effects of GTN on tumor growth also were certificated by the studies of murine transplanted tumors in which tumor growth was significantly inhibited in GTN administered group. All these studies illustrated that GTN possesses potential anticancer activity. doi:10.1016/j.niox.2007.09.082

C38. Plasma levels of oxidative stress markers in patients with B–chronic lymphocytic leukemia I. Zelen, P. Djurdjevic, P. Ristic, I. Jovanovic, V. Jakovljevic, D. Baskic, S. Popovic, N. Arsenijevic Medical Faculty, Sv. Markovica 69, Kragujevac, Serbia Oxidative stress is well-known phenomenon in the body which plays an important role in pathogenesis of various diseases and syndromes as like as for involvement in both initiation and promotion of multistage carcinogenesis. The overproduction of ROS can result in detrimental cellular damage including lipid peroxidation, DNA adduct formation, protein oxidation and enzyme inactivation that ultimately lead to cell death. The main feature of chronic lymphocytic leukemia (CLL) is an accumulation of malignant B-cells with low proliferation activity that escape the fate of apoptosis by a variety of mechanisms. One of the potential mechanisms of defective apoptosis could be irregular oxidative stress. In the present study, we aimed to investigate the parameters of oxidative stress in plasma of patients with CLL. Plasma level of nitric oxide (NO), superoxide anion (O2 ), hydrogen peroxide (H2O2) and malondialdehyde (MDA) were determined spectrophotometrically. Plasma were obtained from heparinized whole blood. CLL patients were staged according to Binet classification. Patients in the A stage of disease (30), 20 patients in the stages B and C of disease and 30 healthy volunteers as a control group were examined. The result showed significantly decreased plasma level of NO in CLL patients of stages B and C of disease compared with control group (13.37 ± 3.10 lM vs 28.18 ± 6.87 lM, p < 0.01). Plasma levels of O2 and H2O2 showed differences without stastistical significance among examined groups. Plasma level of MDA was increased in CLL patients than in the control group (p < 0.01). doi:10.1016/j.niox.2007.09.083