Numerical modelling and experimental verification of thermal effects in living cells exposed to high-power pulses of THz radiation.

Exposure of cells or biological tissues to high-power pulses of terahertz (THz) radiation leads to changes in a variety of intracellular processes. However, the role of heating effects due to strong absorption of THz radiation by water molecules still stays unclear. In this study, we performed numerical modelling in order to estimate the thermal impact on water of a single THz pulse as well as a series of THz pulses. A finite-element (FE) model that provides numerical solutions for the heat conduction equation is employed to compute the temperature increase. A simple expression for temperature estimation in the center of the spot of THz radiation is presented for given frequency and fluence of the THz pulse. It has been demonstrated that thermal effect is determined by either the average power of radiation or by the fluence of a single THz pulse depending on pulse repetition rate. Human dermal fibroblasts have been exposed to THz pulses (with an energy of [Formula: see text] and repetition rate of 100 Hz) to estimate the thermal effect. Analysis of heat shock proteins expression has demonstrated no statistically significant difference ([Formula: see text]) between control and experimental groups after 3 h of irradiation.

Propagation of THz irradiation energy through aqueous layers: Demolition of actin filaments in living cells.

The effect of terahertz (THz) radiation on deep tissues of human body has been considered negligible due to strong absorption by water molecules. However, we observed that the energy of THz pulses transmits a millimeter thick in the aqueous solution, possibly as a shockwave, and demolishes actin filaments. Collapse of actin filament induced by THz irradiation was also observed in the living cells under an aqueous medium. We also confirmed that the viability of the cell was not affected under the exposure of THz pulses. The potential of THz waves as an invasive method to alter protein structure in the living cells is demonstrated.

Exposure Effects of Terahertz Waves on Primary Neurons and Neuron-like Cells Under Nonthermal Conditions.

OBJECTIVE: This study aimed to explore the potential effects of terahertz (THz) waves on primary cultured neurons from 4 rat brain regions (hippocampus, cerebral cortex, cerebellum, and brainstem) and 3 kinds of neuron-like cells (MN9D, PC12, and HT22 cells) under nonthermal conditions. METHODS: THz waves with an output power of 50 (0.16 THz) and 10 (0.17 THz) mW with exposure times of 6 and 60 min were used in this study. Analysis of temperature change, neurite growth, cell membrane roughness, micromorphology, neurotransmitters and synaptic-related proteins (SYN and PSD95) was used to evaluate the potential effects. RESULTS: Temperature increase caused by the THz wave was negligible. THz waves induced significant neurotransmitter changes in primary hippocampal, cerebellar, and brainstem neurons and in MN9D and PC12 cells. THz wave downregulated SYN expression in primary hippocampal neurons and downregulated PSD95 expression in primary cortical neurons. CONCLUSION: Different types of cells responded differently after THz wave exposure, and primary hippocampal and cortical neurons and MN9D cells were relatively sensitive to the THz waves. The biological effects were positively correlated with the exposure time of the THz waves.

Study of the effects of 0.15 terahertz radiation on genome integrity of adult fibroblasts.

The applications of Terahertz (THz) technologies have significantly developed in recent years, and the complete understanding of the biological effects of exposure to THz radiation is becoming increasingly important. In a previous study, we found that THz radiation induced genomic damage in fetal fibroblasts. Although these cells demonstrated to be a useful model, exposure of human foetuses to THz radiation is highly improbable. Conversely, THz irradiation of adult dermal tissues is cause of possible concern for some professional and nonprofessional categories. Therefore, we extended our study to the investigation of the effects of THz radiation on adult fibroblasts (HDF). In this work, the effects of THz exposure on HDF cells genome integrity, cell cycle, cytological ultrastructure and proteins expression were assessed. Results of centromere-negative micronuclei frequencies, phosphorylation of H2AX histone, and telomere length modulation indicated no induction of DNA damage. Concordantly, no changes in the expression of proteins associated with DNA damage sensing and repair were detected. Conversely, our results showed an increase of centromere-positive micronuclei frequencies and chromosomal nondisjunction events, indicating induction of aneuploidy. Therefore, our results indicate that THz radiation exposure may affect genome integrity through aneugenic effects, and not by DNA breakage. Our findings are compared to published studies, and possible biophysical mechanisms are discussed. Environ. Mol. Mutagen. 59:476-487, 2018. © 2018 Wiley Periodicals, Inc.

The interaction between electromagnetic fields at megahertz, gigahertz and terahertz frequencies with cells, tissues and organisms: risks and potential.

Since regular radio broadcasts started in the 1920s, the exposure to human-made electromagnetic fields has steadily increased. These days we are not only exposed to radio waves but also other frequencies from a variety of sources, mainly from communication and security devices. Considering that nearly all biological systems interact with electromagnetic fields, understanding the affects is essential for safety and technological progress. This paper systematically reviews the role and effects of static and pulsed radio frequencies (100-109 Hz), millimetre waves (MMWs) or gigahertz (109-1011 Hz), and terahertz (1011-1013 Hz) on various biomolecules, cells and tissues. Electromagnetic fields have been shown to affect the activity in cell membranes (sodium versus potassium ion conductivities) and non-selective channels, transmembrane potentials and even the cell cycle. Particular attention is given to millimetre and terahertz radiation due to their increasing utilization and, hence, increasing human exposure. MMWs are known to alter active transport across cell membranes, and it has been reported that terahertz radiation may interfere with DNA and cause genomic instabilities. These and other phenomena are discussed along with the discrepancies and controversies from published studies.

[The specific features of the development of metabolic and regenerative processes under the action of low-intensity electromagnetic radiation in radiation exposure conditions (an experimental study)]. / Osobennosti razvitiia metabolicheskikh i regenerativnykh protsessov pri deistvii nizkointensivnykh élektromagnitnykh izluchenii v usloviiakh radiatsionnogo oblucheniia (éksperimental'noe issledovanie).

The experiments on male white rats with the use of biochemical, photo-optical, and electron-microscopic techniques have demonstrated that the use of low-intensity electromagnetic radiation of ultrahigh frequency (EMR UHF) and low-intensity low-frequency magnetic field (MF) during the post-irradiation period (within 21 days after exposure to radiation) enhanced the metabolic and regenerative processes in the testes and liver. It was shown that the application of MF largely intensified the antioxidant activity whereas EMR UHF preferentially stimulated the biosynthetic processes as well as the processes of cellular and intracellular regeneration.

In vivo analysis of THz wave irradiation induced acute inflammatory response in skin by laser-scanning confocal microscopy.

The recent development of THz sources in a wide range of THz frequencies and power levels has led to greatly increased interest in potential biomedical applications such as cancer and burn wound diagnosis. However, despite its importance in realizing THz wave based applications, our knowledge of how THz wave irradiation can affect a live tissue at the cellular level is very limited. In this study, an acute inflammatory response caused by pulsed THz wave irradiation on the skin of a live mouse was analyzed at the cellular level using intravital laser-scanning confocal microscopy. Pulsed THz wave (2.7 THz, 4 µs pulsewidth, 61.4 µJ per pulse, 3Hz repetition), generated using compact FEL, was used to irradiate an anesthetized mouse's ear skin with an average power of 260 mW/cm(2) for 30 minutes using a high-precision focused THz wave irradiation setup. In contrast to in vitro analysis using cultured cells at similar power levels of CW THz wave irradiation, no temperature change at the surface of the ear skin was observed when skin was examined with an IR camera. To monitor any potential inflammatory response, resident neutrophils in the same area of ear skin were repeatedly visualized before and after THz wave irradiation using a custom-built laser-scanning confocal microscopy system optimized for in vivo visualization. While non-irradiated control skin area showed no changes in the number of resident neutrophils, a massive recruitment of newly infiltrated neutrophils was observed in the THz wave irradiated skin area after 6 hours, which suggests an induction of acute inflammatory response by the pulsed THz wave irradiation on the skin via a non-thermal process.

High-power femtosecond-terahertz pulse induces a wound response in mouse skin.

Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. Although a thorough assessment to predict potential concerns has to precede before practical utilization of THz source, the biological effect of THz radiation is not yet fully understood with scant related investigations. Here, we applied a femtosecond-terahertz (fs-THz) pulse to mouse skin to evaluate non-thermal effects of THz radiation. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly mediated by transforming growth factor-beta (TGF-ß) signaling pathways. We validated NFκB1- and Smad3/4-mediated transcriptional activation in fs-THz-irradiated skin by chromatin immunoprecipitation assay. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of TGF-ß. These findings suggest that fs-THz radiation initiate a wound-like signal in skin with increased expression of TGF-ß and activation of its downstream target genes, which perturbs the wound healing process in vivo.

Studying the non-thermal effects of terahertz radiation on E. coli/pKatG-GFP biosensor cells.

Studies of the impact of terahertz radiation on living objects present a significant interest since its use for security systems is currently considered promising. We studied the non-thermal impact of terahertz radiation on E. coli/pKatG-gfp biosensor cells. The Novosibirsk free electron laser (NovoFEL), which currently has the world's highest average and peak power, was used as the source of terahertz radiation. We demonstrated that exposure to terahertz radiation at the wavelengths of 130, 150, and 200 µm and a power of 1.4 W/cm(2) induces changes in green fluorescent protein (GFP) fluorescence values and thus induces the expression of GFP in E. coli/pKatG-gfp biosensor cells. Possible mechanisms of the E. coli response to non-thermal exposure to terahertz radiation are discussed.

Terahertz radiation at 0.380 THz and 2.520 THz does not lead to DNA damage in skin cells in vitro.

The question whether nonionizing electromagnetic radiation of low intensity can cause functional effects in biological systems has been a subject of debate for a long time. Whereas the majority of the studies have not demonstrated these effects, some aspects still remain unclear, e.g., whether high-frequency radiation in the terahertz range affects biological systems. In particular for frequencies higher than 0.150 THz, investigations of the ability of radiation to cause genomic damage have not been performed. In the present study, human skin cells were exposed in vitro to terahertz radiation at two specific frequencies: 0.380 and 2.520 THz. Power intensities ranged from 0.03-0.9 mW/cm(2) and the cells were exposed for 2 and 8 h. Our goal was to investigate whether the irradiation induced genomic damage in the cells. Chromosomal damage was not detected in the different cell types after exposure to radiation of both frequencies. In addition, cell proliferation was quantified and found to be unaffected by the exposure, and there was no increase in DNA damage measured in the comet assay for both frequencies. For all end points, cells treated with chemicals were included as positive controls. These positive control cells clearly showed decreased proliferation and increased genomic damage. The results of the present study are in agreement with findings from other studies investigating DNA damage as a consequence of exposure to the lower frequency range (<0.150 THz) and demonstrate for the first time that at higher frequencies (0.380 and 2.520 THz), nonionizing radiation does not induce genomic damage.

The influence of high intensity terahertz radiation on mammalian cell adhesion, proliferation and differentiation.

Understanding the influence of exposure of biological systems to THz radiation is becoming increasingly important. There is some evidence to suggest that THz radiation can influence important activities within mammalian cells. This study evaluated the influence of the high peak power, low average power THz radiation produced by the ALICE (Daresbury Laboratory, UK) synchrotron source on human epithelial and embryonic stem cells. The cells were maintained under standard tissue culture conditions, during which the THz radiation was delivered directly into the incubator for various exposure times. The influence of the THz radiation on cell morphology, attachment, proliferation and differentiation was evaluated. The study demonstrated that there was no difference in any of these parameters between irradiated and control cell cultures. It is suggested that under these conditions the cells are capable of compensating for any effects caused by exposure to THz radiation with the peak powers levels employed in these studies.

[Changes gas and electrolyte structure of blood under influence terahertz radiations on frequencies nitrogen oxide 150,176-150,664 GHz in the conditions of stress].

Influence terahertz radiations nitrogen oxide frequencies of 150,176 - 150,664 GHz on gas and electrolyte structure of blood of white rats being in condition of sharp stress. It is shown that at 15 minute mode of influence terahertz waves on frequencies nitrogen oxide observe partial restoration of studied indicators gas and electrolyte structure of blood at stress animals. At 30 minute mode of influence the specified waves observe complete recovery of the broken indicators gas and electrolyte blood structure.

In vitro investigation of the biological effects associated with human dermal fibroblasts exposed to 2.52 THz radiation.

BACKGROUND: Terahertz (THz) radiation sources are increasingly being used in military, defense, and medical applications. However, the biological effects associated with this type of radiation are not well characterized. In this study, we evaluated the cellular and molecular response of human dermal fibroblasts exposed to THz radiation. METHODS: In vitro exposures were performed in a temperature-controlled chamber using a molecular gas THz laser (2.52 THz, 84.8 mW cm(-2), durations: 5, 10, 20, 40, or 80 minutes). Both computational and empirical dosimetric techniques were conducted using finite-difference time-domain (FDTD) modeling approaches, infrared cameras, and thermocouples. Cellular viability was assessed using conventional MTT assays. In addition, the transcriptional activation of protein and DNA sensing genes were evaluated using qPCR. Comparable analyses were also conducted for hyperthermic and genotoxic positive controls. RESULTS: We found that cellular temperatures increased by 3°C during all THz exposures. We also found that for each exposure duration tested, the THz and hyperthermic exposure groups exhibited equivalent levels of cell survival (≥90%) and heat shock protein expression (∼3.5-fold increases). In addition, the expression of DNA sensing and repair genes was unchanged in both groups; however, appreciable increases were observed in the genotoxic controls. CONCLUSIONS: Human dermal fibroblasts exhibit comparable cellular and molecular effects when exposed to THz radiation and hyperthermic stress. These findings suggest that radiation at 2.52 THz generates primarily thermal effects in mammalian cells. Therefore, we conclude that THz-induced bioeffects may be accurately predicted with conventional thermal damage models.

[What's new in biomedical applications for Terahertz (THz) technology]. / A la frontière onde-lumière : que peuvent apporter les techniques térahertz (THz) dans le domaine de la santé ?

Terahertz technologies have recently been applied to develop high resolution imaging. Since practical portable systems can be designed, the possibilty has emerged to easily screen for biohazards and concealed objects, a procedure which usually requires remote analysis. Applications of THz are also envisaged in the medical field, because this technology offers a degree of accuracy never reached before in molecule analysis. Skin abnormalities and dental health care are two promising targets of THz applications. Nevertheless, potential hazards and health effects of THz exposure should be monitored carefully, particularly since some data suggest induction of genomic instability.

Behavioral effect of terahertz waves in male mice.

We studied the effect of terahertz waves (3.6 THz, 81.5 micro, 15 mW) on the behavior of mice. The mice perceived terahertz waves even after short-term exposure (15 min). The effect of terahertz waves was maximum in direct contact of the mice with the laser. Increased anxiety of experimental animals was observed on the next day after 30-min irradiation.