Answer to Question #12304 Submitted to "Ask the Experts"

Category: Radiation Effects — Effects on Tissues and Organs

The following question was answered by an expert in the appropriate field:

Q

I have been reading articles about the biological effects of low-dose radiation. I have some thoughts that I am not sure are correct after reading an article by Rothkamm and Löbrich (2003). Here are my questions:

  • The article shows that for doses ranging from 1.2 milligray (mGy) to 200 mGy, there were the same number of DNA double-strand breaks after several days. Does this mean the risks are the same for doses ranging from 1.2 mGy to 200 mGy?
  • The authors state that "After [a] few cell divisions, irradiated cell cultures show nearly the same level of γ-H2AX foci but substantially more micronucleated and apoptotic cells than unirradiated controls . . ." Are micronucleated and apoptotic cells abnormal? Is there risk of having more of these cells compared with controls?
A

You have hit on a topic of great interest and discussion in modern radiation biology: How to interpret experimental results we get from studying radiation effects in cells and molecules in terms of risk of a negative effect in whole organisms (like cancer in humans). My interpretation is that the results of this paper suggest that low doses of radiation do not increase cancer risk.

The paper you referenced (Rothkamm and Löbrich 2003) was very influential, and they looked at the repair of a particular type of DNA damage caused by radiation exposure. DNA is made up of two strands wrapped together and connected by bases. Radiation can break both strands of the DNA, and these kinds of double-strand breaks can be particularly challenging for cells to repair themselves. When this damage occurs, and the cell commits to repair the damage, DNA-repair proteins are recruited to the site of the break to begin the repair process of stitching the DNA strands back together.

One of these repair proteins is known as γ-H2AX, and in the paper you cited the authors attached a fluorescent marker to this protein so that it is visible under a microscope. This paper demonstrated a critical point: That γ-H2AX is a marker for DNA-repair activity in cells, and by watching γ-H2AX we are actually watching the repair of DNA double-strand breaks. The researchers exposed the cells to radiation, and then they watched what happened with γ-H2AX.

So what did they find? It depended on whether the cells were actively dividing or not. Most of the cells in your body are just going about their business, and are not actively dividing—blood cells carrying oxygen to tissues, muscle cells contracting and relaxing, etc. When cells that aren't supposed to be dividing decide to ignore the stop signs and begin to divide, bad things happen—this is cancer. Unrepaired DNA breaks are not so important in nondividing cells. The cells usually can still go about their business. But unrepaired DNA breaks in cells that are dividing can be a problem because those breaks allow cells to ignore the stop signs, begin dividing uncontrollably, and develop into cancer.

The authors found that after low doses of radiation, cells didn't repair some DNA double-strand breaks for a long time. No problem—the cells just went about their business. This doesn't present any risk as long as the cells aren't dividing. But then they made these cells start dividing; and in response, they saw the cells carrying unrepaired DNA double-strand breaks commit suicide (apoptosis). This sounds worrisome, but it is actually a defense mechanism that cells use very effectively. Dead cells don't go on to become cancerous; so when the authors observed that cells with DNA double-strand breaks committed suicide (became apoptotic), these potentially troublesome cells were deleted from the cell population.

They also saw more micronucleated cells, which are cells that are carrying a particular kind of error in their chromosomes that are also fatal to the cell. Micronucleated cells also represent cells that cannot successfully divide, and they are eventually deleted. They saw that when these irradiated cells were allowed to divide, the levels of DNA double-strand breaks returned to the levels they saw in cells that were not exposed to radiation. This indicates that the risk of developing cancer was not increased by the radiation exposure.

The authors concluded, "The results presented are in contrast to current models of risk assessment that assume that cellular responses are equally efficient at low and high doses . . ." This is a vitally important conclusion, because our current radiation protection regulations are based on the assumptions that (1) radiation risk is directly related to radiation dose, (2) the same things happen at high and low doses, and (3) every dose of radiation, no matter how small, carries some risk. This paper indicates that these assumptions are not accurate, and at least in this experiment, low doses of radiation did not increase risk.

Now, some caution is in order. This is one paper, and this is not settled science. This paper experimented on cells in a bottle, not on whole people. There is some uncertainty on how to apply results in cells to risks of cancer in humans. But this paper suggests that when we design studies that directly look at risks in human populations, we should consider and test for the possibility that low doses of radiation do not increase risk. It also suggests that we should discuss whether our current regulations on low doses of radiation provide any benefits that outweigh the costs.

Brant Ulsh, PhD, CHP

Reference

Rothkamm K, Löbrich M. Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 100: 5057–5062; 2003.

Ask the Experts is posting answers using only SI (the International System of Units) in accordance with international practice. To convert these to traditional units we have prepared a conversion table. You can also view a diagram to help put the radiation information presented in this question and answer in perspective. Explanations of radiation terms can be found here.
Answer posted on 10 January 2018. The information posted on this web page is intended as general reference information only. Specific facts and circumstances may affect the applicability of concepts, materials, and information described herein. The information provided is not a substitute for professional advice and should not be relied upon in the absence of such professional advice. To the best of our knowledge, answers are correct at the time they are posted. Be advised that over time, requirements could change, new data could be made available, and Internet links could change, affecting the correctness of the answers. Answers are the professional opinions of the expert responding to each question; they do not necessarily represent the position of the Health Physics Society.