ROS production in response to high-power microwave pulses induces p53 activation and DNA damage in brain cells: Radiosensitivity and biological dosimetry evaluation

Abstract

Background: Pulsed high-power microwave (HPM) has many applications and is constantly being researched to expand its uses in the future. As the number of applications grows, the biological effects and safety level of pulsed HPM become a serious issue, requiring further research.Objective: The brain is regarded as the most vulnerable organ to radiation, raising concerns about determining an acceptable level of exposure. The effect of nanosecond pulses and the mechanisms underlying HPM on the brain has not been studied. For the first time, we observed the effect of pulsed 3.5 GHz HPM on brain normal astrocytes and cancer U87 MG cells, as well as the likely mechanisms involved.Methods: To generate 3.5 GHz HPM, an axial virtual cathode oscillator was constructed on pulsed power generator “Chundoong”. The cells were directly exposed to HPM (10, 25, 40, and 60) pulses (1 mJ/pulse), with each pulse delivered after 1 min of charging time to evaluate the dose dependent effects.Results: A strong electric field (∼23 kV/cm) of HPM irradiation primarily causes the production of reactive oxygen species (ROS), altering cell viability, mitochondrial activity, and cell death rates in U87 and astrocytes at certain dosages. The ROS generation in response to HPM exposure was primarily responsible for DNA damage and p53 activation. The hazardous dosage of 60 pulses is acknowledged as having damaging effects on brain normal cells. Interestingly, the particular 25 pulses exhibited therapeutic effects on U87 cells via p53, Bax, and Caspase-3 activation.Conclusion: HPM pulses induced apoptosis-related events such as ROS burst and increased oxidative DNA damage at higher dosages in normal cells and specific 25 pulses in cancer U87. These findings are useful to understand the physiological mechanisms driving HPM-induced cell death, as well as the safety threshold range for HPM exposure on normal cells and therapeutic effects on cancer U87. As HPM technology advances, we believe this study is timely and will benefit humanity and future research.

Effect of Plasma On-Time with a Fixed Duty Ratio on Reactive Species in Plasma-Treated Medium and Its Significance in Biological Applications

“…The Alamar blue assay for measuring cell cytotoxicity was performed at two different duty ratios of 10% and 36%, and the results were shown in Figure 9 . The U87-MG cell line is the most well known, and it is utilized to study brain cancers [ 41 ]. The viability of the U87-MG with a 10% duty ratio was shown in Figure 9 a–d for treatment times of PTM that were 1, 3, 5, and 7 min, respectively.…”

The Small RNA Landscape in NSCLC: Current Therapeutic Applications and Progresses

“…Despite advances, resistance to conventional therapies, relapses and poor prognosis are very frequent. Innovative anti-cancer strategies, including nanosecond microwave pulses, have been applied to inhibit other types of cancer [ 141 ] and can be potentially used for NSCLC, even if no data on this kind of application are available so far.…”

Screening of Cu4O3 NPs efficacy and its anticancer potential against cervical cancer

“…Recently, Abu‐Serie et al suggested that higher oxygen intensity of Cu 4 O 3 NPs could activate apoptosis 43 . High ROS production can cause DNA damage that is dependent on various apoptosis‐inducing mechanisms such as, modulation in p53 expression and MMP, and cytochrome C release from mitochondria 50–52 . Furthermore, because GSH lacks S‐glutathiolated protection from caspase‐3, which is activated by proteolytic cleavage, the redox properties of Cu in Cu 4 O 3 NPs may produce reactive hydroxyl radicals that deplete GSH and trigger apoptosis 10,43 .…”

“…43 High ROS production can cause DNA damage that is dependent on various apoptosis-inducing mechanisms such as, modulation in p53 expression and MMP, and cytochrome C release from mitochondria. [50][51][52] Furthermore, because GSH lacks S-glutathiolated protection from caspase-3, which is activated by proteolytic cleavage, the redox properties of Cu in Cu 4 O 3 NPs may produce reactive hydroxyl radicals that deplete GSH and trigger apoptosis. 10,43 ROS can also be an attractive target molecules for cancer treatment in addition to being a significant component in the apoptosis intrinsic or extrinsic pathway.…”