Targeting cancer cells by magnetic field modified radical reactions and ionizing radiation - TARZAN
Project lead: Jukka Luukkonen, PhD (UEF)
Radiotherapy project lead: Jan Seppälä, Chief Physicist (KUH)
Radiotherapy has long been an important treatment option for cancer with about half of the patients receiving the modality. This therapy approach uses ionizing radiation to eliminate cancerous cells by evoking direct or indirect damage to DNA. Direct damage to DNA produces radical cations and anions, while indirect effects are caused by radicals that form during the radiolysis of surrounding molecules. As radicals are key players in the radiation-induced damage, an additional manipulation of their levels, exploited also in chemotherapy, offers an effective therapeutic strategy to increase the effect of radiation treatment.
According to World Health Organization (WHO), the radical pair mechanism is one the most likely biophysical mechanism for explaining the possible adverse effects of weak magnetic fields. This quantum mechanical theory states that chemical reactions with radical pairs as transient intermediates are sensitive to weak magnetic interactions. For radical pairs generated from diamagnetic precursors, this mechanism is considered to increase the free radical yield in low field strengths (at about < 1 mT) and to decrease them in high field intensities.
Over the last 40 years, the radical pair mechanism has become theoretically well established and shown in chemical systems, but its role in biology is less well known. However, as radiotherapy causes a large burst of radical reactions, it offers an exceptional opportunity for the radical pair mechanism to modify radical yields and cause substantial biological effects.
The proposed project will be a unique attempt to enhance the efficiency of radiotherapy by combining theoretical work on radicals and experimental magnetic field research. The experimental approach will employ isolated DNA, multiple cancer cell lines and two mouse xenograft models. The focus will be on finding the most effective field parameters (field strength, timing, direction, duration, and frequency) for modifying radical reactions and using this knowledge to improve tumor control by radiation treatment. In addition, possible adverse effects associated with magnetic field-enhanced radiotherapy will be studied in healthy cells/tissues. The long-term vision is that the ground-breaking work performed in the proposed project will form the basis for the development of novel medical devices to treat cancer.
This pioneering study will combine theoretical and experimental work to determine the most effective MF parameters for radiotherapy enhancement.
The specific objectives of this project are:
- To make MF strength and direction predictions to cause 1) maximum radical yield resulting from DNA-radical reactions or 2) large-scale decreases or increases in radicals at the cellular level.
- To exploit the predictions to identify optimal MF parameters for potentiating radiotherapy in vitro.
- To investigate the possible adverse effects from the designed treatment with healthy cells/tissues.
- To verify the plausibility of in vitro findings in an animal model.
Group members - UEF
Jukka Luukkonen University Lecturer , Department of Environmental and Biological Sciences, Radiation and Chemical...