Due to radiation-induced immune depression and development of pathologies such as cancer, there is increasing urgency to identify radiomitigators that are effective when administered after radiation exposure. The main goal of this study was to determine the radiomitigation capacity of MnTE-2-PyP[Mn(III) tetrakis (N-ethylpyridinium-2-yl) porphyrin], a superoxide dismutase (SOD) mimetic, and evaluate leukocyte parameters in spleen and blood. C57BL/6 mice were total-body exposed to 2 Gy γ-rays (Co-60), i.e., well below a lethal dose, followed by subcutaneous implantation of 5 3 10(5) RM-9 prostate tumor cells and initiation of MnTE-2-PyP treatment (day 0); interval between each procedure was 1-2 h. The drug was administered daily (12 times). Tumor progression was monitored and immunological analyses were performed on a subset per group on day 12. Animals treated with MnTE-2-PyP alone had significantly slower tumor growth compared to mice that did not receive the drug (P < 0.05), while radiation alone had no effect. Treatment of tumor-bearing mice with MnTE-2-PyP alone significantly increased spleen mass relative to body mass; the numbers of splenic white blood cells (WBC) and lymphocytes (B and T), as well as circulating WBC, granulocytes, and platelets, were high compared to one of more of the other groups (P < 0.05). The results show that MnTE-2-PyP slowed RM-9 tumor progression and up-regulated immune parameters, but mitigation of the effects of 2 Gy total-body irradiation were minimal.
Written by:
Mehrotra S, Pecaut MJ, Freeman TL, Crapo JD, Rizvi A, Luo-Owen X, Slater JM, Gridley DS Are you the author?
Department of Radiation Medicine, Radiation Research Laboratories, Loma Linda University and Medical Center, Loma Linda, CA, U.S.A.
Reference: Technol Cancer Res Treat. 2012 Mar 28.
PubMed Abstract
PMID: 22475066