Determining Individual Risk of Ionizing Radiation

How would you like to be able to determine each individual patient’s risk when it comes to ionizing radiation? A biophysicist from Lawrence Berkeley National Laboratory in California is working on technology that could be used to determine exactly that.

Sylvain Costes, PhD, a biophysicist with Berkeley Lab’s Life Science Division, is also CEO of a start-up called Exogen Biotechnology, which is working on the issue of assessing and tracking human genetic repair capacity.

The idea behind Exogen, Costes said, is to take human blood specimens, expose it to radiation, see how quickly that radiation damage can be repaired, and characterize the response. Does that person repair damage from radiation like the average population, or at a slower rate? And if so, is there anything that can be done about it?

Consequently, physicians could use that information to determine an individual’s risk when exposed to different imaging modalities.

Costes’ work at Exogen is related to research he and colleagues at Lawrence Berkeley have been doing on the impact differing levels of ionizing radiation have on DNA repair mechanisms.

Costes’ and his colleagues published a paper recently in the Proceedings of the National Academy of Sciences in which they determined - through a combination of time-lapse imaging and mathematical modeling of human breast cells - that cell repair mechanisms are effective in dealing with exposure to low doses of radiation, but tend to get overwhelmed if they have to handle larger radiation doses.

In the article, “Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells,” the researchers concluded that their work “casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation.”

Costes and his colleagues hypothesized that double strand breaks (when the DNA double helix is completely severed) cluster into regions of the nucleus he called “DNA repair centers” as radiation exposure increases.

So, according to Costes, these repair centers can get overwhelmed when cells receive doses high enough to cause multiple double strand breaks. This can result in some of those double strand breaks being incorrectly rejoined, which can lead to cancer.

Costes compared the process to responding to an automobile accident.

“If you have an accident, you’ll have a tow truck come and bring your car to the garage, where the mechanic has all the correct tools and can fix the problem correctly,” he said. “It’s very efficient.”

But that system is a problem when you have a massive crash on the highway and you have to take 200 cars to the local garage,” he explained. “Obviously the garage is not going to be able to handle that well.

“That’s very similar to what happens with DNA breaks.”

Costes pointed out that while human beings evolved in an environment where they were exposed to radiation, that exposure was not comparable to that received, for example, from radiotherapy or computed tomography.

“Under normal conditions our bodies are very well poised to repair those breaks [caused by exposure to low doses of radiation], so a few breaks here and there are quickly fixed, and you move on,” he explained. “But if suddenly you get bombarded with these breaks all at once then the repair system won’t work as well and it increases the probability of misrepair.”

So what are the implications of this research on imaging?

“Right now there is no clear cut answer,” Costes said. “But, with a low dose of radiation - say 1 centigray (cGy) and perhaps up to 5 centigray - the cells should repair that damage very well, so the risk from imaging is very low.”

There is a caveat and it involves that individual variability, which is related to the work Costes is doing at Exogen.

According to Costes, there is a good correlation between the repair kinetic of DNA and cancer risk in animals. “The DNA repair kinetic seems to be a good marker for a risk from ionizing radiation, both in terms of toxicity and in terms of cancer incidence,” Costes said. “And now we think this is related to the clustering phenomenon. So we are hypothesizing that when you have clustering you have a higher risk of misrepair and therefore a higher probability of having cancer as well.”

“We don’t know how many people have this kind of behavior we’ve described,” he said, adding that some may have a very strong clustering behavior, which means they may be a higher risk from imaging.

“Individuality is probably a very big factor in determining response [to radiation exposure],” Costes said. “So we need further study to determine how much variability there is between people.”

But, ideally, it could be possible to determine an individual’s risk factor concerning exposure to ionizing radiation, Costes said, and even serve as a method for assessing radiation risk for the population as a whole.

“Maybe,” he said, “it will lessen our concerns about exposure to low levels of radiation.”