The results are found to be consistent with the history of safe use in MR scanning, but not with current safety guidelines. For future safety concepts, we suggest to use thermal dose models instead of temperatures or SAR. Special safety concerns for patients with impaired thermoregulation (e.g., the elderly, diabetics) should be addressed.
Background
Administration of amplitude modulated 27·12 MHz radiofrequency electromagnetic fields (AM RF EMF) by means of a spoon-shaped applicator placed on the patient's tongue is a newly approved treatment for advanced hepatocellular carcinoma (HCC). The mechanism of action of tumour-specific AM RF EMF is largely unknown.
Methods
Whole body and organ-specific human dosimetry analyses were performed. Mice carrying human HCC xenografts were exposed to AM RF EMF using a small animal AM RF EMF exposure system replicating human dosimetry and exposure time. We performed histological analysis of tumours following exposure to AM RF EMF. Using an agnostic genomic approach, we characterized the mechanism of action of AM RF EMF.
Findings
Intrabuccal administration results in systemic delivery of athermal AM RF EMF from head to toe at levels lower than those generated by cell phones held close to the body. Tumour shrinkage results from differentiation of HCC cells into quiescent cells with spindle morphology. AM RF EMF targeted antiproliferative effects and cancer stem cell inhibiting effects are mediated by Ca
2+
influx through Ca
v
3·2 T-type voltage-gated calcium channels (CACNA1H) resulting in increased intracellular calcium concentration within HCC cells only.
Interpretation
Intrabuccally-administered AM RF EMF is a systemic therapy that selectively block the growth of HCC cells. AM RF EMF pronounced inhibitory effects on cancer stem cells may explain the exceptionally long responses observed in several patients with advanced HCC.
Fund
Research reported in this publication was supported by the National Cancer Institute's Cancer Centre Support Grant award number P30CA012197 issued to the Wake Forest Baptist Comprehensive Cancer Centre (BP) and by funds from the Charles L. Spurr Professorship Fund (BP). DWG is supported by R01 AA016852 and P50 AA026117.
In this paper, we present the detailed life-time dosimetry analysis for rodents exposed in the reverberation exposure system designed for the two-year cancer bioassay study conducted by the National Toxicology Program of the National Institute of Environmental Health Sciences. The study required the well-controlled and characterized exposure of individually housed, unrestrained mice at 1900 MHz and rats at 900 MHz, frequencies chosen to give best uniformity exposure of organs and tissues. The wbSAR, the peak spatial SAR and the organ specific SAR as well as the uncertainty and variation due to the exposure environment, differences in the growth rates, and animal posture were assessed. Compared to the wbSAR, the average exposure of the high-water-content tissues (blood, heart, lung) were higher by ~4 dB, while the low-loss tissues (bone and fat) were less by ~9 dB. The maximum uncertainty over the exposure period for the SAR was estimated to be <49% (k=2) for the rodents whereas the relative uncertainty between the group was <14% (k=1). The instantaneous variation (averaged over 1 min) was <13% (k=1), which is small compared to other long term exposure research projects. These detailed dosimetric results empowers comparison with other studies and provides a reference for studies of long-term biological effects of exposure of rodents to RF energy.
In this paper, fetal exposure to uniform magnetic fields (MF) with different polarizations is quantified at 50 Hz. Numerical computations were performed on high-resolution pregnant models at 3, 7, and 9 months of gestational age (GA), that distinguish a high number of fetal tissues. Fetal whole-body and tissue-specific induced electric fields (E) and current densities (J) were analyzed as a function of both the extremely low frequency magnetic field (ELF-MF) polarization and GA. Additionally, the induced field variation due to changes in fetal position was analyzed by means of two new pregnant models. The uncertainty budget due to the grid resolution was also calculated. Finally, the compliance of the fetal exposure to the ICNIRP Guidelines was checked. A fetal exposure matrix was built at 50 Hz, which could be used to further investigate possible interaction mechanisms between ELF-MF and the associated health risk. Some specific findings were: (1) the induced fields increased with GA; (2) the maxima E were found in skin and fat tissues at each GA; (3) fetal tissue-specific exposure was modified as a function of GA and polarization; (4) the change of the fetal position in the womb significantly modified the induced E in some fetal tissues; (5) the induced fields were in compliance with ICNIRP Guidelines and the results were quite below the permitted threshold limit.
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