New precision device could advance low-dose radiation cancer research
CLEMSON, South Carolina — Radiation is a powerful weapon against some types of cancer, but using the therapy is still more like a shotgun approach than a surgical strike, shooting a tumor with large doses of broad-spectrum X-rays that damage healthy tissue and cause side effects.
In a study published in the journal PLOS ONE, a team of Clemson University bioengineering and physics students and faculty describe an irradiation fluorescence system they developed that could accelerate research in delivering very specific types of radiation in controlled doses. They also showed that low doses of specific, controlled radiation are safe for healthy cells.
Sources of radiation are everywhere — sunlight, trace amounts of radioactive elements in the soil, medical imaging and outer space, where radiation is a concern for astronauts. At its most basic, radiation is energy released in the form of subatomic particles. Each atom has its own wavelength and energy; collectively, they comprise a spectrum of radiation.
If radiation were a rainbow of colors, the Clemson team was able to use and measure a very specific shade of the rainbow at a specific low dose consistently. Previous radiation research has lacked detailed information, making the science difficult to replicate and verify.
“In general, researchers haven’t been too worried about the exact energies, wavelengths and dosages of radiation,” said Delphine Dean, an associate professor of bioengineering at Clemson and the senior author of the paper.
Elements absorb specific wavelengths of energy and release others, a process called fluorescence. In their study, the Clemson researchers bounced X-rays off a small plate of iron. The iron absorbed some wavelengths and emitted others onto a dish of fibroblast cells from a well-established mouse line provided by the National Institutes of Health.
For 24 hours after being irradiated, the cells grew slower than cells that didn’t receive radiation. By the third day, however, the irradiated cells were growing at a much faster rate than the non-radiated cells. The researchers suggest cells slowed growth as a protective measure to minimize DNA damage, then sped up the cell cycle to overcome the damage. By the fifth day, both irradiated and non-irradiated cells were growing at the same rate.
Previous research has shown that cancer cells have a difficult time repairing themselves after low doses of radiation. But the pause and rapid rebound by the healthy cells in the Clemson project was surprising and encouraging, Dean said.
“When we first started working on this, I actually made the students redo the experiments several times because I thought that it didn’t make sense that the cells would start to proliferate faster after irradiation. But it was so nicely repeatable that we knew it was really something there. That’s a lot to do with our system. We know exactly the dose, dose rate and energy every time we do the experiment so there’s no question that what we were seeing was real,” she said.
What made the Clemson study different from others started with a collaboration between bioengineering and physics students.
“I am impressed by how far our students were able to push this research considering that small overlap of the two fields. On the other hand, this makes our collaboration exciting and the results unique and valuable for the scientific community,” said Endre Takacs, associate professor of atomic and medical physics in Clemson’s College of Science.
Katelyn Truong, a senior at Clemson and first author on the paper, said the collaboration between bioengineering and physics was “fundamental” in developing the low-dose X-ray source and performing analytical tests.
“The physics students contributed tremendously by really delving into calculations behind the X-ray spectra analysis. Specifying precise doses and keeping these doses consistent for the cells would have been impossible without their help,” Truong said.
Together, the students determined that using specific, well-characterized radiation was essential. Then, they overcame the challenges of creating a device that can fit within an incubator about the size of a mini-fridge.
“Everything had to fit inside the box that was heated and humid, which is not the way precision physics studies are typically done. It took a bunch of clever reengineering of our first prototype irradiator to do that. The physics team machined the parts and everything is custom so that it can fit and still irradiate the cell cultures,” Takacs said.
“In order to calculate the amount of radiation reaching the cells, the elementary physical processes of the interaction of x-rays with different materials needed to be considered. This information went into the design of the fluorescent setup, the container holding the cell and the built-in monitoring equipment,” Takacs said.
“We’re really hoping this (PLOS ONE) paper gets other research groups to set up similar irradiation systems where the dose, energy, dose rate, etc., are well-characterized. This will help the field so that it will be easier to compare results between groups,” Dean said.
Suzanne Bradley, Bryana Baginski, Joseph Wilson, Leon Zheng and R. Kevin Wilson also were authors of the paper.
The study was funded through the Clemson Creative Inquiry student research program and an NSF CAREER Award to Dean.
This material is based upon work supported by the National Science Foundation under Grant No. NSF CBET CAREER 1245609. Any opinions, findings and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the view of the National Science Foundation.