Induction of genomic instability, oxidative processes, and mitochondrial activity by 50 Hz magnetic fields in human SH-SY5Y neuroblastoma cells

摘要

Epidemiological studies have suggested that exposure to 50 Hz magnetic fields (MF) increases the risk of childhood leukemia, but there is no mechanistic explanation for carcinogenic effects. In two previous studies we have observed that a 24-h pre-exposure to MF alters cellular responses to menadione-induced DNA damage. The aim of this study was to investigate the cellular changes that must occur already during the first 24 h of exposure to MF, and to explore whether the MF-induced changes in DNA damage response can -lead to genomic instability in the progeny of the exposed cells. In order to answer these questions, human SH-SY5Y neuroblastoma cells were exposed to a 50-Hz, 100-muT MF for 24 h, followed by 3-h exposure to menadione. The main finding was that MF exposure was associated with increased level of micronuclei, used as an indicator of induced genomic instability, at 8 and 15 d after the exposures. Other delayed effects in MF-exposed cells included increased mitochondrial activity at 8 d, and increased reactive oxygen species (ROS) production and lipid peroxidation at 15 d after the exposures. Oxidative processes (ROS production, reduced glutathione level, and mitochondrial superoxide level) were affected by MF immediately after the exposure. In conclusion, the present results suggest that MF exposure disturbs oxidative balance immediately after the exposure, which might explain our previous findings on MF altered cellular responses to menadione-induced DNA damage. Persistently elevated levels of micronuclei were found in the progeny of MF-exposed cells, indicating induction of genomic instability.