The proliferative response of the neuroblastoma line NB69 to a 100 µT, 50 Hz magnetic field (MF) has been shown mediated by activation of the MAPK-ERK1/2 pathway. This work investigates the MF effect on the cell cycle of NB69, the participation of p38 and c-Jun N-terminal (JNK) kinases in the field-induced proliferative response and the potential involvement of reactive oxygen species (ROS) in the activation of the MAPK-ERK1/2 and -p38 signaling pathways. NB69 cultures were exposed to the 100 µT MF, either intermittently for 24, 42 or 63 h, or continuously for periods of 15 to 120 min, in the presence or absence of p38 or JNK inhibitors: SB203580 and SP600125, respectively. Antioxidant N-acetylcysteine (NAC) was used as ROS scavenger. Field exposure induced transient activation of p38, JNK and ERK1/2. The MF proliferative effect, which was mediated by changes in the cell cycle, was blocked by the p38 inhibitor, but not by the JNK inhibitor. NAC blocked the field effects on cell proliferation and p38 activation, but not those on ERK1/2 activation. The MF-induced proliferative effects are exerted through sequential upregulation of MAPK-p38 and -ERK1/2 activation, and they are likely mediated by a ROS-dependent activation of p38.

We previously reported that intermittent exposure to a 50‑Hz magnetic field (MF) at 100 µT stimulates cell proliferation in the human neuroblastoma cell line NB69. The present study aimed to investigate whether the magnetic field-induced growth promotion also occurs at a lower magnetic flux density of 10 µT. To this purpose, NB69 cells were subjected for 42 h to intermittent exposure, 3 h on/3 h off, to a 50‑Hz MF at a 10 or 100 µT magnetic flux density. The field exposure took place either in the presence or in the absence of the antiproliferative agent retinoic acid. At the end of the treatment and/or incubation period, the cell growth was estimated by hemocytometric counting and spectrophotometric analysis of total protein and DNA contents. Potential changes in DNA synthesis were also assessed through proliferating cell nuclear antigen (PCNA) immunolabeling. The results confirmed previously reported data that a 42-h exposure to a 50‑Hz sine wave MF at 100 µT promotes cell growth in the NB69 cell line, and showed that 10 µT induces a similar proliferative response. This effect, which was significantly associated and linearly correlated with PCNA expression, was abolished by the presence of retinoic acid in the culture medium.

In vitro exposure to power frequency magnetic fields (MF) has been reported to influence cell proliferation and differentiation. However, the nature of the response of different human cancer cell types to these fields has not been sufficiently characterized. The present work investigates the response of two proliferating human cell lines of neuroblastoma (NB69) and hepatocarcinoma (HepG2) to a 42 h, intermittent treatment with a weak, 100 µT, 50 Hz MF, alone or in combination with 0.5 µM all-trans-retinol (ROL), a retinoid currently applied in oncostatic therapies. In each experimental replicate the cell samples were submitted to one of the following treatment combinations: MF+/ROL+, MF+/ROL-, MF-/ROL+ or MF-/ROL-. The proliferative response was determined by cell counting (Trypan blue exclusion), BrdU incorporation and by spectrophotometric analysis of total protein and DNA content. The results show that when administered separately, the two treatments, MF and ROL, significantly enhanced cell proliferation in both cell lines. In NB69 simultaneous administration of MF and ROL induced an additive effect on cell proliferation, associated to increased DNA content. By contrast, in HepG2 the ROL-induced cell proliferation and increased protein content were partially blocked by simultaneous exposure to MF. Taken together, these data show that both agents, a weak MF and ROL at a low concentration, induce proliferative responses in the two assayed human cell lines. However, significant differences were observed between the responses of the two cellular species to the combined treatment with ROL and MF, indicating that the mechanisms underlying the cellular response to each of the two agents can mutually interact in a manner that is cell type-specific.