Radiation and a Metalloporphyrin Radioprotectant in a Mouse Prostate Tumor Model

• Published in: Anticancer research 2007-09, Vol.27 (5A), p.3101-3109
• Main Authors: Gridley, Daila S, Makinde, Adeola Y, Luo, Xian, Rizvi, Asma, Crapo, James D, Dewhirst, Mark W, Moeller, Benjamin J, Pearlstein, Robert D, Slater, James M
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; B-Lymphocytes - drug effects; B-Lymphocytes - radiation effects; Biological and medical sciences; Body Weight - drug effects; Body Weight - radiation effects; Combined Modality Therapy; Disease Models, Animal; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Killer Cells, Natural - drug effects; Killer Cells, Natural - radiation effects; Leukocyte Count; Male; Medical sciences; Metalloporphyrins - pharmacology; Mice; Mice, Inbred C57BL; Nephrology. Urinary tract diseases; Organ Size - drug effects; Organ Size - radiation effects; Prostatic Neoplasms - blood; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - radiotherapy; Radiation-Protective Agents - pharmacology; Spleen - anatomy & histology; Spleen - drug effects; Spleen - pathology; Spleen - radiation effects; T-Lymphocytes - drug effects; T-Lymphocytes - radiation effects; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 0250-7005; 1791-7530

Background: Antioxidants have the potential to protect normal tissues against radiation-induced damage, but must not protect tumor cells during radiotherapy. The major objectives were to determine whether a metalloporphyrin antioxidant affects prostate tumor response to radiation and identify possible mechanisms of interaction. Materials and Methods: C57BL/6 mice with RM-9 tumor were treated with manganese (III) meso-tetrakis(1,3-diethylimidazolium-2-yl)porphyrin (MnTDE-2-ImP) and 10 gray (Gy) radiation. Tumor volume was quantified and a subset/group was evaluated for hypoxia-inducible factor-1α (HIF-1α), bone marrow-derived cell populations and cytokines. Results: The addition of MnTDE-2-ImP transiently increased tumor response compared to radiation alone. The group receiving drug plus radiation had reduced intratumoral HIF-1α and decreased capacity to secrete TNF-α, whereas production of IL-4 was increased. There were no toxicities associated with combination treatment. Conclusion: The results demonstrate that MnTDE-2-ImP did not protect the RM-9 prostate tumor against radiation; instead, radiation effectiveness was modestly increased. Possible mechanisms include reduction of radiation-induced HIF-1α and an altered cytokine profile.