Human Cryptochrome Mediates Oxidative Stress Responses Modulated by Static and Electromagnetic Fields in Doxorubicin-Treated Cells

Abstract

Cryptochromes (CRYs) have been suggested to involve in the magnetic sensing for navigation of migratory birds in response to Earth’s magnetic fields. Magnetic fields (MFs) through wireless penetration change the cell physiology by effect on physicochemical reactions. Here, we aimed to investigate the behavior of HEK 293T cells overexpressing human CRY-based magnetoreception complexes undergo doxorubicin (DOX) treatment and exposure to moderate intensity static magnetic field (SMF) and extremely low frequency-pulsed electromagnetic field (ELF-PEMF). The ability of this magnetosensor is depended on CRY-photoreceptor proteins that complemented with putative magnetosensor proteins (MagR). The results indicate that magnetic sensitivity of CRY-based magnetosensor can effects on the intracellular reactive oxygen species (ROS) production and cell growth, cell cycle progression and expression of DNA damage-related genes due to treatment of DOX, SMF and ELF-PEMF. Our findings show that ROS accumulation significantly decreased in the cells expressing CRY/MagR complexes in response to all treatments, and also cell viability is decreased in contrast to MFs exposure. In addition, magnetosensitive complexes mediated the upregulation of genes in the base excision repair (BER) pathway including ITPA in presence of SMF as well as MTH1 in presence of ELF-PEMF in the DOX treated-cells. Furthermore, CRY/MagR induced a remarkable cell cycle arrest at G0/G1 phase in the all treatments. These results demonstrated that CRY/MagR complexes modify the DNA damage responses during genotoxic stresses by controlling the cell cycle progression and ROS levels. Therefore, our data suggest that CRY-based magnetosensitive complexes can increase the cytotoxic effects of DOX even when SMF and/or ELF-PEMF exposure were provided, exclusively.