Terahertz Pulses Simultaneously Kills Skin Tissue, Increases Tumor-Suppressing Proteins

New research performed on lab-grown human skin suggests that short but powerful bursts of THz radiation may both cause DNA damage and increase the production of proteins that help the body fight cancer. The findings, which are the result of a collaboration between physicists at the University of Alberta (Edmonton, Canada) and molecular biologists at the University of Lethbridge (Lethbridge, Canada) was published March 18, 2013, in the Optical Society’s (OSA) open-access journal Biomedical Optics Express.

“While these investigations of the biological effects of intense THz pulses are only just beginning,” said Dr. Lyubov Titova, with the University of Alberta and a member of the research team, “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.”

THz photons, similar to their longer wavelength cousins in the microwave range, are not strong enough to disrupt the chemical ties that bind DNA together in the nucleus of cells. These waves, however, have just the right frequency to galvanize water molecules, causing them to vibrate and generate heat, which is why microwave ovens are so effective at cooking food. For this reason, it was believed that heat-related injuries were the primary risks posed by THz radiation exposure.

Recent theoretic studies, however, suggest that intense THz pulses of picosecond (one trillionth of a second) duration may directly affect DNA by amplifying natural vibrations (so-called “breathing” mode) of the hydrogen bonds that bind together the two strands of DNA. As a result, “bubbles” (openings in DNA strands) can form. According to the researchers, this brought up the question if intense THz pulses can destabilize DNA structure enough to cause DNA strand breaks.

As shown in earlier animal cell culture studies, THz exposure may indeed affect biologic function under specific conditions such as high power and extended exposure. There is, however, a huge gap between animal research and conclusions that can be drawn about human health.

In a first of its kind study, the Canadian researchers exposed laboratory-grown human skin tissue to intense pulses of THz electromagnetic radiation and have detected 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 may suggest that DNA damage in human skin arising from intense picosecond THz pulse exposure could be quickly and effectively repaired, therefore lessening the risk of carcinogenesis.

The researchers used a skin tissue model made of healthy, human-derived epidermal and dermal cells. This tissue is able to undergo mitosis and is metabolically active, thus providing a suitable platform for assessing the effects of exposure to high intensity THz pulses on human skin. For their study, Dr. 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. They then examined the sample for the presence of phosphorylated H2AX, which “flags” the DNA double-strand break site and attracts cellular DNA repair machinery to it.

“The increase in the amount of phosphorylated H2AX in tissues exposed to intense THz pulses compared to unexposed controls indicated that DNA double strand breaks were indeed induced by intense THz pulses,” noted Dr. Titova. Once DNA breaks occur, they can ultimately lead to tumors if unrepaired. “This process,” she continued, “is very slow and cells have evolved many effective mechanisms to recognize damage, 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.”

The researchers validated that these cellular repair mechanisms were taking place by detecting an elevated presence of multiple proteins that play vital roles in DNA repair, including protein p53 (frequently 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 indicate that exposure to intense THz pulses activates cellular processes that repair DNA damage. However, the researchers noted, it is too soon to make forecasts on the long-term implications of exposure.

“In our study we only looked at one moment in time—30 minutes after exposure,” Dr. 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 Canadian researchers hope to study the potential therapeutic effects of intense THz radiation exposure to see if directed treatment with intense THz pulses can become a new approach to combat cancer.

Related Links:
University of Alberta
University of Lethbridge