Clinical Potential of EPR Spectroscopy in Assessing Radiation Resistance in Pathogens and Tumors

Clinical Potential of EPR Spectroscopy in Assessing Radiation Resistance in Pathogens and Tumors

Electron paramagnetic resonance (EPR) spectroscopy has emerged as a valuable tool for characterizing the resistance of pathogens and cancer cells to ionizing radiation. Gamma radiation generates reactive oxygen species (ROS) through radiolysis, which in turn induces oxidative stress in organisms. These ROS damage proteins, the primary indicator of cellular survivability, through oxidation, leading to reduced or lost functionality^1,2. The primary cause of oxidative protein damage during irradiation is superoxide, formed when oxygen gains an extra electron. Superoxide is effectively neutralized by manganous (Mn²⁺) antioxidants (H-Mn), which accumulate in various cell types, compared to large manganous accumulating proteins (L-Mn). EPR spectroscopy has identified Mn antioxidant levels in prokaryotes, fungi, cultured cancer cells, and whole organisms like nematodes as the strongest biological markers of ionizing radiation resistance in living cells³.

This study highlights the effectiveness of EPR in assessing radioresistance in Borrelia burgdorferi, an Mn-dependent bacterium that causes Lyme Disease, as part of an investigation into the potential development of an irradiated Lyme Disease vaccine⁴. Cells were cultured in BSK-H media and grown to a concentration of approximately 10⁶ cells/mL. Samples were irradiated to determine the dose required to achieve 90% population reduction (D10). These irradiated samples were compared to a set of non-irradiated samples for EPR analysis, which provides the percentages of HMn and LMn (fH). Despite high Mn/Fe ratio, polyploid B. burgdorferi is radiosensitive, with a survival-limit of less than 1 kGy, indicating potential for irradiated vaccine development.

Additionally, we explore the potential of EPR in assessing the radiation resistance of tumors. We propose that EPR analysis of a biopsy sample could provide insights into a tumor’s radiation resistance, offering valuable information for customizing a targeted radiation or chemotherapy treatment plan.

Bibliography

1. Daly MJ. A new perspective on radiation resistance based on Deinococcus radiodurans. Nat Rev Microbiol. 2009 Mar;7(3):237-45. doi: 10.1038/nrmicro2073. Epub 2009 Jan 27. PMID: 19172147.
2. Daly MJ, Gaidamakova EK, Matrosova VY, Vasilenko A, Zhai M, et al. 2007. Protein oxidation implicated as the primary determinant of bacterial radioresistance. PLoS Biol 5:e92
3. Sharma A, Gaidamakova EK, Grichenko O, Matrosova VY, Hoeke V, et al. 2017. Across the tree of life, radiation resistance is governed by antioxidant Mn(2+), gauged by paramagnetic resonance. Proc Natl Acad Sci U S A 114:E9253-E60
4. Tobin, Gregory J et al. “A novel gamma radiation-inactivated sabin-based polio vaccine.” PloS one vol. 15,1 e0228006. 30 Jan. 2020