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Experimental and Systems Biology Studies of the Molecular Basis for the Radioresistance of Prostate Carcinoma Cells

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Abstract

Molecular mechanisms for the gamma-ionizing radiation (IR) resistance of human prostate cancer cells, PC-3, are not quite clear. Since the low-LET-IR effects are primarily manifested by the generation of reactive oxygen species (ROS), the IR-induced expressions both of ROS-metabolizing antioxidant enzymes, such as Mn- and CuZn superoxide dismutases (SODs) and catalase (Cat), and of the transcriptional nuclear factor-kappaB (NF-κB) were explored. A substantial increase in the concentrations of SODs was observed in the cells irradiated by 10 and 20 Gy relative to those irradiated by 0 and 2 Gy, while the Cat and NF-κB expressions were found to be fairly stable. A system biology model was developed to shed more light on how MnSOD affects the biological state of cells depending upon the production of H2O2. By raising the initial presence of MnSOD in the 0.7–10 μM concentration range, the time-dependent concentrations of H2O2 for various initial levels of MnSOD were contrasted. The radioresistance of PC-3 cells is suggested to be associated with the positive, feed-forward vicious circle established between the H2O2-mediated elevation of MnSOD expression.

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Acknowledgments

This work was supported by the Projects 143042B and 143016B (Prof. Petar M. Mitrasinovic, Ph.D.) financed by the Ministry of Science of the Republic of Serbia. The authors gratefully acknowledge the reviewers for valuable comments.

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Authors and Affiliations

  1. Laboratory of Molecular Biology and Endocrinology, VINČA Institute of Nuclear Sciences, P.O. Box 522-090, 11000, Belgrade, Serbia

    Ana Niciforovic, Jelena Djordjevic, Miroslav Adzic, Vesna Vucic & Marija B. Radojcic

  2. Department of Biophysics, Center for Multidisciplinary Studies, University of Belgrade, Kneza Viseslava 1a, 11030, Belgrade, Serbia

    Petar M. Mitrasinovic

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  1. Ana Niciforovic
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  2. Jelena Djordjevic
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  3. Miroslav Adzic
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  5. Petar M. Mitrasinovic
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  6. Marija B. Radojcic
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Correspondence to Petar M. Mitrasinovic or Marija B. Radojcic.

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Petar M. Mitrasinovic and Marija B. Radojcic equally contributed to this paper.

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Niciforovic, A., Djordjevic, J., Adzic, M. et al. Experimental and Systems Biology Studies of the Molecular Basis for the Radioresistance of Prostate Carcinoma Cells. Ann Biomed Eng 36, 831–838 (2008). https://doi.org/10.1007/s10439-008-9457-4

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  • DOI: https://doi.org/10.1007/s10439-008-9457-4

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