Does Photofrin II Combined with a Radio-Adaptive Dose Lead to a Synergistic or Additive Effect after Ionising Irradiation In Vitro?

Abstract

Background: The radiosensitizing effect of Photofrin II has been demonstrated in vitro and in animal models, even in tumor models known to be highly radioresistant, such as glioblastoma and bladder carcinoma. Radio-adaptive doses are also known to lead to an augmented cell or tissue reaction. The aim of this study was to investigate potential synergistic or additive effects when combining the two methods in vitro for an improved therapeutic concept in bladder cancer. Material and Methods: RT4 human bladder carcinoma cell line and HCV29 human bladder epithelium cells were seeded and incubated with various concentrations of Photofrin II. The cells were additionally irradiated with ionizing radiation (0.05 Gy/2 Gy/0.05 Gy + 2 Gy). Cells without Photofrin II incubation and irradiation served as controls. The cell survival was evaluated. Results: The survival rate of both cell lines, RT4 and HCV29, did not differ significantly when incubated with a non-toxic concentration of Photofrin II and exposed to a pre-irradiation dose of 0.05 Gy prior to the 2 Gy radiation fraction, compared to cells exposed to Photofrin II plus a 2 Gy ionizing radiation. Conclusion: The combination of both methods did neither demonstrate a synergistic or additive effect nor did it lead to a negative influence of both modulating factors in an in vitro setting.

Share and Cite:

M. Schaffer, A. Balandin, B. Ertl-Wagner, P. Schaffer, L. Bonavina, A. Hofstette and U. Kulka, "Does Photofrin II Combined with a Radio-Adaptive Dose Lead to a Synergistic or Additive Effect after Ionising Irradiation In Vitro?," Journal of Cancer Therapy, Vol. 2 No. 4, 2011, pp. 595-600. doi: 10.4236/jct.2011.24079.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] W. H. McBride and H. R. Withers, “Biologic Basis of Radiation Therapy,” In: C. A. Perez and L. W. Brady, Eds., Principles and Practice of Radiation Oncology, Lippincott Williams and Wilkins, Philadelphia, 2004, pp. 96-136.
[2] T. H. Wassermann and J. D. Chapman, “Radiation Response Modulation,” In: C. A. Perez and L. W. Brady, Eds., Principles and Practice of Radiation Oncology, Lippincott Williams and Wilkins, Philadelphia, 2004, pp. 663-679.
[3] I. Patties, J. Jahns, G. Hildebrandt, R. D. Kortmann and A. Glasow, “Additive Effects of 5-Aza-2’-deoxycytidine and Irradiation on Clonogenic Survival of Human Medulloblastoma Cell Lines,” Strahlentherapie und Onkologie, Vol. 185, No. 5, 2009, pp. 331-338. doi:10.1007/s00066-009-1956-1
[4] L. Cohen and S. Schwartz, “Modification of Radiosensitivity by Porphyrins II. Transplanted Rhabdomyosarcoma in Mice,” Cancer Research, Vol. 26, 1966, pp. 1769-1773.
[5] M. Schaffer, P. Schaffer, M. Vogesser, B. Ertl-Wagner, et al., “The Application of Photofrin II as a Specific Radiosensitzing Agent, in Patients with Bladder-Cancer, Report of Two Cases,” Photochemical & Phobiological Science, Vol. 1, 2002, pp. 686-689. doi:10.1039/b203732g
[6] C. J. Byrne, L. V. Morshallsay and A. D. Wand, “The Chemical Composition of Photofrin,” Journal of Photochemistry and Photobiology B: Biology, Vol. 6, 1990, pp. 13-27.
[7] U. Kulka, M. Schaffer, P. M. Schaffer, et al., “Photofrin as an Efficient Radiosensitizer in an in Vitro Cell Survival Assay,” Biochemical & Biophysical Research Comunications, Vol. 311, No. 1, 2003, pp. 98-103. doi:10.1016/j.bbrc.2003.09.170
[8] U. Kulka, M. Schaffer, P. M. Schaffer, et al., “Untersuchungen zum Mechanismus der radiosensitivierenden Wirkung von Photofrin II,” Strahlentherapie und Onkologie, Vol. 181, No. 1, 2005, p. 104.
[9] M. Schaffer, P. M. Schaffer, L. Corti, G. Sotti, A. Hofstetter, G. Jori and E. Dühmke, “Photofrin II as an Efficient Radiosensitising Agent in an Experimental Tumour,” Onkologie, Vol. 24, No. 5, 2001, pp. 482-485. doi:10.1159/000055130
[10] M. Schaffer, P. M. Schaffer, L. Corti, et al., “Photofrin as a Specific Radiosensitising Agent for Tumours: Studies in Comparison to Other Porphyrins, in an Experimental in Vivo Model,” Journal of Photochemistry and Photobiology B: Biology, Vol. 66, 2002, pp. 157-164.
[11] M. Schaffer, B. Ertl-Wagner, P. M. Schaffer, et al., “The Application of Photofrin II as a Sensitizing Agent for Ionizing Radiation—A New Approach in Tumour Therapy?” Current Medicinal Chemistry, Vol. 12, No. 10, 2005, pp. 763-771. doi:10.2174/0929867053764653
[12] M. Schaffer, U. Kulka and P. M. Schaffer, “The Role of Radical Derivatives of High Reactivity in the Radiosensitizing Action of Photofrin II,” Journal of Porphyrins and Phthalocynines, Vol. 10, No. 12, 2006, pp. 1398-1402. doi:10.1142/S1088424606000776
[13] P. M. Schaffer, U. Kulka and B. Ertl-Wagner, “The Influence of Oxygen on the Radiosensitizing Activity of Photofrin II and Hypericin,” Journal of Porphyrins and Phthalocyanines, Vol. 11, No. 10, 2007, pp. 1-6. doi:10.1142/S1088424607000849
[14] G. Olivieri, J. Bodycote and S. Wolff, “Adaptive Response of Human Lymphocytes to Low Concentrations of Radioactive Thymidine,” Science, Vol. 223, No. 4636, 1984, pp. 594-597. doi:10.1126/science.6695170
[15] M. A. Coleman, E. Yin, L. E. Peterson, D. Nelson and K. Sorensen, “Low-Dose Irradiation Alters the Transcript Profiles of Human Lymphoblastoid Cells Including Genes Assosiated with Cytogenetic Radioadaptive Response,” Radiation Research, Vol. 164, No. 4, 2005, pp. 369-382. doi:10.1667/RR3356.1
[16] P. Cramers, P. Atanasova and H. Vrolijk, “Pre-exposere to Low Doses: Modulation of X-Ray-Induced DNA Damage and Repair?” Radiation Research, Vol. 164, No. 4, 2005, pp. 383-390. doi:10.1667/RR3430.1
[17] S. Sadekova, S. Lehnert and T. Y. K. Chow, “Induction of PBP74/Mortalin/Grp75, a Member of the hsp70 Family, by Low Doses of Ionizing Radiation: A Possible Role in Induced Radioresistance,” International Journal of Radiation Biology, Vol. 72, No. 6, 1997, pp. 653-660. doi:10.1080/095530097142807
[18] M. S. Sasaki, Y. Ejima, A. Tachibana, et al., “DNA Damage Response Pathway in Radioadaptive Response,” Mutation Research, Vol. 504, No. 1-2, 2002, pp. 101-118. doi:10.1016/S0027-5107(02)00084-2
[19] R. Okazaki, A. Ootsuyama and T. Norimura, “TP53 and TP53-Related Genes Associated with Protection from Apoptosis in the Radioadaptive Response,” Radiation Research, Vol. 167, No. 1, 2007, pp. 51-57. doi:10.1667/RR0623.1
[20] M. Schaffer, S. B. Schwarz and U. Kulka, “Adaptive Doses of Irradiation—An Approach to a New Therapy Concept for Bladder Cancer?” Radiation and Environmental Biophysics, Vol. 43, No. 4, 2004, pp. 271-276. doi:10.1007/s00411-004-0256-5
[21] S. B. Schwarz, P. M. Schaffer and U. Kulka, “The Effect of Radio-Adaptive Doses on HT29 and GM637 Cell,” Radiation Oncology, Vol. 3, 2008, p. 12. doi:10.1186/1748-717X-3-12
[22] M. A. Bean, H. Pees, J. E. Fogh, H. Grabstald and H. F. Oettgen, “Cytotoxicity of Lymphocytes from Patients with Cancer of the Urinary Bladder: Detection by a 3Hproline Microtoxicity Test,” International Journal of Cancer, Vol. 14, No. 2, 1974, pp. 186-197. doi:10.1002/ijc.2910140207
[23] J. R. W. Masters, P. J. Hepburn, L. Walker et al., “Tissue Culture Model of Transitional Cell Carcinoma: Characterization of Twenty-Two Human Urothelial Cell Lines,” Cancer Research, Vol. 46, 1986, pp. 3630-3636.
[24] P. Balermpas, M. Hambek, O. Seitz, C. R?del and C. Weiss, “Combined Cetuximab and Reirradiation for Locoregional Recurrent and Inoperable Squamous Cell Carcinoma of the Head and Neck,” Strahlentherapie und Onkologie, Vol. 185, No. 12, 2009, pp. 775-781. doi:10.1007/s00066-009-2092-7
[25] K. Dittmann, C. Mayer and H. P. Rodemann, “Nuclear EGFR as Novel Therapeutic Target Insights into Nuclear Translocation and Function,” Strahlentherapie und Onkologie, Vol. 186, No. 1, 2010, pp. 1-6. doi:10.1007/s00066-009-2026-4
[26] J. D. Shadley and S. Wolff, “Very Low Doses of X-Rays can Cause Human Lymphocytes to Become Less Susceptible to Ionising Radiation,” Mutagenesis, Vol. 2, No. 2, 1987, pp. 95-96. doi:10.1093/mutage/2.2.95
[27] J. D. Shadley, “Chromosomal Adaptive Response in Human Lymphocytes,” Radiation Research, Vol. 138, No. 1, 1994, pp. 9-12. doi:10.2307/3578750
[28] A. M. Ueno, D. B. Vannais, D. L. Gustafson, J. C. Wong and C. A. Waldren, “A Low, Adaptive Dose of Gamma- Rays Reduced the Number and Altered the Spectrum of S1-Mutants in Human-Hamster Hybrid AL Cells,” Mutation Research, Vol. 358, No. 2, 1996, pp. 161-169. doi:10.1016/S0027-5107(96)00117-0
[29] S. Venkat, S. K. Apte, R. C. Chaubey and P. S. Chauhan, “Radioadaptive Response in Human Lymphocytes in Vitro,” Journal of Environmental Pathology, Toxicology and Oncology, Vol. 20, 2001, pp. 165-175.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.