Terahertz radiation is rapidly finding important uses in medical diagnostics, security and scientific research, but at what cost to our health? New research on lab-grown human skin suggests that short, powerful bursts of THz radiation may damage DNA, but also increase the production of proteins that help the body fight cancer. “While these investigations of the biological effects of intense THz pulses are only just beginning, the fact that intense THz pulses can induce DNA damage but also DNA repair mechanisms in human skin tissue suggests that intense THz pulses need to be evaluated for possible therapeutic applications,” said University of Alberta researcher Lyubov Titova. A special gel-based analysis used to detect specific proteins shows elevated levels of gamma H2AX, the marker for DNA damage. It shows that there are elevated levels of the protein in the THz-pulse exposed tissues compared with control samples that were not exposed. Courtesy of Biomedical Optics Express. As with their longer-wavelength cousins in the microwave range, THz photons are not energetic enough to break the chemical bonds that bind DNA together in the cell’s nucleus. These waves, however, have just the right frequency to energize water molecules, causing them to vibrate and produce heat. For this reason, it was believed that heat-related injuries were the principal risks posed by THz radiation exposure. Recent theoretical studies, however, suggest that intense THz pulses of picosecond duration may directly affect DNA by amplifying natural vibrations of the hydrogen bonds that bind together the two strands of DNA. As a result, “bubbles” or openings in DNA strands can form. According to the researchers, this raised the question: “Can intense THz pulses destabilize DNA structure enough to cause DNA strand breaks?” Earlier animal cell culture studies have shown that THz exposure may affect biological function under specific conditions, such as high-power and extended exposure, but it is difficult to draw the same conclusion for humans. Now, physicists and molecular biologists from the universities of Alberta and Lethbridge have exposed laboratory-grown human skin tissue to intense pulses of THz electromagnetic radiation to detect the telltale signs of DNA damage through a chemical marker known as phosphorylated H2AX. At the same time, they observed THz pulse-induced increases in the levels of multiple tumor suppressor and cell-cycle regulatory proteins that facilitate DNA repair. This could suggest that DNA damage in human skin arising from intense picosecond THz exposure could be quickly and efficiently repaired, minimizing the risk of carcinogenesis. A skin tissue model made of normal, human-derived epidermal and dermal cells was used because it can undergo mitosis and is metabolically active, providing an appropriate platform for assessing the effects of exposure to high-intensity THz pulses on human skin. For their study, Titova and her colleagues exposed the skin tissue to picosecond bursts of THz radiation at levels far above what would typically be used in current real-world applications. Next, they studied the sample for the presence of phosphorylated H2AX, which “flags” the DNA double-strand break site and attracts cellular DNA repair machinery to it. In cell nucleus, DNA is wound around cores made of histone proteins. One of the proteins, H2AX, plays an important role in recognition of DNA damage. This schematic shows what the researchers suspect is happening to DNA molecules when exposed to strong pulses of THz radiation. The upper row is immediately following the pulse when the strand of DNA is broken. The lower portion shows the H2AX molecules around the break site 1 to 3 min later, after they are “flagged” by the attachment of a phosphate group, which signals that DNA damage has taken place. Courtesy of Ayesheshim K. Ayesheshim. “The increase in the amount of phosphorylated H2AX in tissues exposed to intense THz pulses compared with unexposed controls indicated that DNA double-strand breaks were indeed induced by intense THz pulses,” Titova said. Once DNA breaks occur, they can eventually lead to tumors if unrepaired. “This process is very slow, and cells have evolved many effective mechanisms to recognize damage, to pause cell cycle to allow time for damage to be repaired, and — in case repair is unsuccessful — to prevent damage accumulation by inducing apoptosis, or programmed cell death of the affected cell.” These cellular repair mechanisms taking place were confirmed by detecting an elevated presence of multiple proteins that play vital roles in DNA repair, including protein p53 (often called “a guardian of the genome”); p21, which works to stop cell division to allow time for repair; protein Ku70, which helps reconnect the broken DNA strands; and several other important cell proteins with known tumor-suppressor roles. These observations indicated that exposure to intense THz pulses activates cellular mechanisms that repair DNA damage. However, the researchers say it is too soon to make predictions on the long-term implications of exposure. “In our study, we only looked at one moment in time — 30 minutes after exposure,” Titova said. “In the future, we plan to study how all the observed effects change with time after exposure, which should allow us to establish how quickly any induced damage is repaired.” The investigators will next explore THz radiation exposure’s potential therapeutic effects to see if directed treatment can become a new tool to fight cancer. The findings were published in Biomedical Optics Express (doi: 10.1364/BOE.4.000559). For more information, visit: www.ualberta.ca