Science Interviews


Mon, 26th Jan 2015

Anti-radiation antidote

Professor Gabor Tigyi, University of Tennessee

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When the reactor at the Chernobyl nuclear station exploded, some people werepills exposed to massive doses of radiation resulting in lethal damage to the DNA in their cells. Now scientists in the US have developed a drug that can protect against this level of radiation exposure, even if itís administered hours after the radiation dose. Apart from being useful in the event of a nuclear accident, the breakthrough might hold the key to reducing the side effects of radiotherapy for patients undergoing cancer treatments, as the University of Tennessee's Gabor Tigyi explained to Chris Smith...

Gabor - Radiation is everywhere. Itís there not only in the nuclear reactors but also in the nuclear bombs. But those of us who travel long distances on an airplane are exposed to a higher level of radiation than at the surface of the Earth. This radiation interacts with our cells and above certain levels, it can cause damage. This damage usually leads to breaks in our DNA and unless the cell somehow can fix and restore the blueprint, it may die. So, repairing DNA has to be very efficient.

Chris - So, how are you approaching that? What have you done to try to boost the rate at which cells can put damage to their DNA right?

Gabor - We actually learned something by studying the very simple molecule called lysophosphatidic acid. Generally, in the course of blood clotting that enhance DNA repair and most importantly, increases cell survival after various harmful stimuli. It has a very short half-life in our bodies and itís not like a drug that you can take once a day and then have a long lasting effect. So, what our research group has tackled over the years is to design a stabilised drug-like analogue of this natural substance that can do all the things that the natural substance does Ė increase DNA repair, self-proliferation, and cell survival. This is in essence what has been accomplished.

Chris - And the chemical youíve got, your drug candidate, how have you tested it? Just in a dish or have you actually tried this for real in an animal?

Gabor - Yes, indeed. We had extensive studies carried out in the mice under various radiation injury scenarios Ė one that mimics damage done by radiation to the bone marrow and also, in another setting to the intestine. In both cases, the compound was highly effective.

Chris - Would these animals or the level of radiation to which these animals have been exposed be equivalent to people who were working at Chernobyl or equivalently say, Fukushima in Japan where the nuclear meltdown occurred in the last few years?

Gabor - Well actually, radiation levels at the base of the reactor at Fukushima produced about a 10 grey radiation dose to those who are the robots that actually went into the vicinity. Our animals were exposed to 16 grey Ė itís a deadly level of radiation - yet, we had very nice survival outcomes after drug treatment.

Chris - We often use radiation therapeutically and people who have cancer, we can zap the cancer with a blast of radio therapy and this can be very effective. But it does have side effects. It damages healthy tissue in the process. Do you think we could use the approach you have come up with to mitigate some of the damage done to healthy tissue in a person having anti-cancer radio therapy treatment, so that they donít have so many side effects?

Gabor - Indeed. What we are hoping to achieve in the next few years is to actually attenuate the collateral damage that is inflicted by the therapeutic use of radiation. For example, if you have breast cancer, radiation therapy is often used and thus, causes scarring and other side effects in the skin. So, thatís something that we would like to try to tackle.


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Interesting but I feel somewhat improbable. As I understand it, radiation damage is principally caused by free water radicals (produced by the radiation ionising cytoplasm) interfering with the hydrogen bonding of mitotic DNA. Once you have induced e.g. crosslinking errors, it is difficult to see how any chemical agent can unscramble them without causing further damage and errors.

I guess you could find a chemical agent that preferentially kills cells that are replicating abnormally quickly, and this would prevent carcinogenesis, but the mention of a threshold dose suggests the new drug works on acute (deterministic) radiation effects rather than stochastic ones, so it must be bringing dead cells back to life.

Hmmm. alancalverd, Wed, 4th Feb 2015

I read one of the interviewee's articles, entitled "Mitigation of radiation injury by selective stimulation of the LPA2 receptor" (Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Volume 1831, Issue 1, January 2013, Pages 117Ė125)

From what I understood of the article, the drugs prevent apoptosis of affected cells--the drugs do not induce repair of damaged DNA. I guess that after radiation exposure there are cells that are still potentially functional, but damaged enough, or close enough to damaged cells, that they would naturally undergo apoptosis (cell death). If enough cells in an organism undergo apoptosis, the organism can no longer function, and dies.

My guess is that these drugs prevent acute, short term symptoms of radiation poisoning, but may actually increase cancer rates, by not allowing highly damaged cells to die... chiralSPO, Wed, 4th Feb 2015

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