Effect of Magnetic Field During Radiotherapy on Double-Strand DNA Breaks and Cell Proliferation on Prostate, Cervical, and Breast Cancer Cells

Abstract

MR-guided radiotherapy (RT) using MR-Linacs is an emerging technology. It allows for real-time tracking of targets and organs-at-risk to deliver RT with high precision. However, the biological effect of a strong magnetic field on cancer cells during RT is not well known, with conflicting data reported in literature. In this study, the effects of a magnetic field during RT on resulting DNA double-stand breaks (DSBs) and cell viability were investigated. Human cancer cells from prostate (PC3), cervix (HeLa), and breast (MCF-7, MB 231, T47D) were cultured used DMEM media with 10% FBS. A Varian CLINAC (Palo Alto, CA, USA) 6 MV beam was used to deliver RT to a 96 well plate. The plate was mounted in a custom 0.21 T magnetic solenoid coil with the magnetic field oriented parallel to the RT beam. DSBs were assessed via γ- H2AX assay: cells were fixed 24 hours post 2 Gy of RT and immunostained with fluorescent γ- H2AX antibody probe, and the number of foci per cell was determined using a Molecular Imaging MetaXpress High Content Imaging Platform (San Jose, CA, USA). Cell viability was determined using Alamar Blue fluorescence assay at 72 hours post RT using calibrated dilution of cells per cell line at 2, 4, 6, and 8 Gy dose. Each RT experiment was done with and without the magnetic field turned on (RT and MRT, respectively). For PC3, fewer cells expressed >6 foci of DSBs under MRT than RT (58% vs 63%, p<0.01. In contrast, more cells demonstrated >6 DSB foci under MRT than RT for HeLa (18% vs 16%, p<0.01), MCF-7 (2.7% vs 0.1%, p<0.001), MB 231 (8.2% vs 1.5%, p<0.001), and T47D (2.3% vs 1.4%, p=0.027). Cell viability following 2 - 8 Gy of radiation for all cell lines demonstrated no significant difference between MRT or RT. Preliminary results suggest differences in the quantity of DSBs were observed under MRT vs RT at 24 hours post-2Gy RT with a 0.21 T field, with a less proliferative cell line (PC3) demonstrating lower DSBs under MRT than RT, and the other highly proliferative cell lines showing the opposite trend. This did not manifest in altered cell viability under the doses of RT or magnetic field strength tested. Future studies aimed at exploring differing biological effects under different magnetic field strengths and cell lines should be explored.