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Credit Ayesheshim K Ayesheshim

New research performed on lab-grown human skin suggests that short but powerful bursts of terahertz (THz) electromagnetic 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 collaboration between physicists at the University of Alberta (Canada) and molecular biologists at the University of Lethbridge (Canada), are published in the article “Intense THz pulses cause H2AX phosphorylation and activate DNA damage response in human skin in vivo” in the Optical Society’s (OSA) open-access journal Biomedical Optics Express.

THz photons, like their longer wavelength cousins in the microwave range, are not energetic enough to break the chemical bonds that bind DNA together in the nucleus of cells. These waves, however, have just the right frequency to energise water molecules, causing them to vibrate and produce heat, which is why microwave ovens are so efficient at cooking food. 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 1 picosecond (i.e., 1 trillionth of a second) duration may directly affect DNA by amplifying natural vibrations (the so-called “breathing” mode) 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 destabilise DNA structure enough to cause DNA strand breaks?

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 (one of the histone proteins). At the same time, they observed THz pulse-induced increases in the levels of multiple tumour 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 efficiently repaired, minimising the risk of carcinogenesis.

In cell nuclei, DNA is wound around cores made of histone proteins. One of the histone proteins, H2AX, plays 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 minutes later after they are flagged by the attachment of a phosphate group, which signals that DNA damage has taken place. Credit: Ayesheshim K. Ayesheshim

The researchers used a skin-tissue model made of normal, human-derived epidermal and dermal cells. This tissue is able to undergo mitosis (cell division) and is metabolically active, thus providing an appropriate platform for assessing the effects of exposure to high intensity THz pulses on human skin. For their study, Lyubov Titova, from the University of Alberta and a member of the research team, 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 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.

“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,” observed Titova. Once DNA breaks occur, they can eventually lead to tumours if unrepaired. “This process,” she continued, “is very slow and cells have evolved many effective mechanisms to recognise 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.”

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 to control samples that weren’t exposed. Credit: Biomedical Optics Express.

The researchers confirmed 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 (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 tumour-suppressor roles. These observations indicate that exposure to intense THz pulses activates cellular mechanisms that repair DNA damage. However, the researchers note, 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 Canadian researchers hope to explore the potential therapeutic effects of intense THz radiation exposure to see if directed treatment with intense THz pulses can become a new tool to fight cancer.

Labels: Canada,medicine,physics,biotechnology

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