Terahertz Stimulate Specific Signaling Pathways in Human Cells
Ibtissam Echchgadda1, Jessica E. Grundt2, Cesario Z. Cerna1, Caleb C. Roth1, Bennett L. Ibey2, Gerald J. Wilmink2
1General Dynamics Information Technology, JBSA Fort Sam Houston, TX 78234 USA
2Air Force Research Laboratory, 711th Human Performance Wing, Human Effectiveness Directorate, Bioeffects Division, Radio Frequency Bioeffects Branch, JBSA Fort Sam Houston, TX 78234 USA
Abstract—Terahertz (THz) waves can influence gene expression and consequently could affect the cell phenotypic properties. In this study, we evaluated the cell response of human cells exposed to THz radiation. We show that 2.52 THz frequency alters the expression of specific messenger ribonucleic acids (mRNAs), microRNAs and intracellular signaling pathways, which were not observed in a thermally-matched bulk-heating control.
I. INTRODUCTION
In recent years, many THz imaging and sensing technologies have been developed, which have revolutionized the landscape of this rapidly evolving research discipline. These innovative technologies are now finding increasing use for a host of applications. A few examples include medical and biological imaging, security screening, quality control of food and pharmaceuticals, ultrafast computing, and wireless communication [1]. The emergence of these new THz-based applications has resulted in an increased interest in the biological effects associated with this frequency range. To date, several investigations have been performed to better understand the bioeffects generated from THz radiation. The data from these reports indicate that THz can exert a diverse range of effects at the organism, tissue, and cell level [1]. It is reported that THz waves can directly impact the structure, functional activity, and dynamics of Deoxyribonucleic acid (DNA) and proteins. Thereby, THz radiation can significantly influence gene expression and consequently can affect the biochemical and phenotypic properties of the exposed cells. In fact, recent studies demonstrated that THz radiation can cause gene transcriptional alterations in various cell types [2], [3]. Moreover, experiments also showed that exposure of mouse stem cells to THz radiation changed the expression of specific genes resulting in a change in cell morphology [3].
When living cells are exposed to high-power THz, an appreciable amount of energy is deposited on the surface of these molecules. Therefore, THz-induced bioeffects are believed to be primarily mediated by the temperature rise generated during exposure (i.e., hyperthermal effects). However, given that THz radiation can strongly interact with water and macromolecules, whose lifetime scales are on the order of a picosecond, it has also long been argued that THz radiation can exert its effects through coherent excitations and/or nonlinear resonance mechanisms [1]. The question of whether cells exposed to high-power THz radiation exhibited comparable responses as those of conventional hyperthermia still remains unanswered. In this study, we compared the global effect of a continuous-wave, single-frequency, 2.52 THz and a thermally-matched, bulk-heating (BH) on the expression of mRNAs and microRNAs (miRNAs). Full gene
expression profiling was performed using microarray GeneChips® (Asuragen Services, Austin, TX) and evaluated using bioinformatics analysis tools.
II. RESULTS
In our initial set of experiments, we sought to determine the temperature rise that would be generated in cells exposed to 2.52 THz radiation (υ = 2.52 THz, Φ = 636 mWcm-2) for 40 min duration. Our computational and empirical dosimetric data showed that the temperature increased 6 °C during exposure. We then used this value to set the thermally- matched BH protocol at 44 °C for 40 min.
To get a comprehensive view of the transcriptional response to THz irradiation, we exposed Jurkat cells to 2.52 THz frequency or BH and used microarray GeneChips® to examine mRNA and miRNAs expression changes in each exposure condition versus sham (unexposed cells). For interpretation of data, we employed the Ingenuity Pathways Analysis tool (IPA, version 8.7, Ingenuity® Systems Inc., Redwood City, CA) as well as other web-based resources such as the GeneCards Human Gene Database and The HUGO Gene Nomenclature Committee.
In Fig. 1, we display the total number of significantly differentially expressed mRNA and miRNAs transcripts that we identified in THz- and BH-exposed cells.
2014-M5-P8.1_Echchgadda