Cancer Research UK scientists have identified a new molecule that seems to play a crucial role in protecting cells against radiation.
The discovery, reported in the journal Nature, should help scientists understand how exposure to radiation can cause cancer.
Experts believe it may be useful for predicting how our bodies would respond following exposure to radioactivity released either accidentally, or deliberately from a potential nuclear attack or ‘dirty bomb’.
The research also has important implications for cancer treatment. Targeting cancer cells with drugs to inactivate the molecule could make them much more sensitive to the effects of radiotherapy.
In human cells, exposure to radiation sets off an emergency response system, which patches up mutated genes or kills off cells that have suffered irreparable damage. This system is a key defence against the development of cancer.
Scientists at the Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology at Cambridge University grew cells in the laboratory and studied the effects of exposing them to beams of radiation.
Researchers found that a mystery protein molecule – which they have called MDC1 – plays a key role in helping cells to detect and repair radiation damage. When they knocked out the activity of the molecule, cells lost their ability to mount the necessary responses to radiation, making them susceptible to accumulating a host of genetic errors.
Cancer Research UK’s Professor Steve Jackson of the Wellcome Trust/Cancer Research UK Institute, team leader on the study, says: “The molecule we’ve discovered seems to play a crucial role in recognising genetic damage and setting into motion the chain of events that will lead to its repair. By helping cells to patch up radiation damage, we speculate that it is acting as a key barrier against the development of cancer.
“Understanding what happens within our cells when they’re pounded with radiation is important for a whole range of reasons, not least for predicting the effects of cancer radiotherapy. In addition, it may suggest how the effects of radiation might be curtailed following a possible nuclear attack.
“Some individuals may be naturally more resistant to the radioactivity than others, and studying these people could give us an important insight into ways of reducing the risk of cancer from radioactive exposure.”
The MDC1 molecule works together with three others – called MRE11, RAD50 and NBS1 – to detect damage to DNA and prevent cells from dividing until their genes have been repaired. After exposure to radiation, MDC1 helps guide its partners to places within the DNA where breaks have occurred, flagging up the damage and kick-starting the process of gene repair.
Doctors take advantage of the damaging effects of radiation with radiotherapy, which works by causing lethal damage to the DNA of cancer cells. Preventing MDC1 from working could therefore be a valuable way of making the treatment more effective.
Prof Jackson adds: “There’s a real potential here to improve radiotherapy by inactivating the molecule and leaving cancer cells sensitised to radiation.
“At the moment, we’re investigating how much of the new molecule is found within tumours, so that we can see whether differences in MDC1 levels may influence clinical outcome.”
Sir Paul Nurse, Cancer Research UK’s Chief Executive, says: “Our bodies are constantly being bombarded by background levels of radioactivity, but early on in the history of life, cells evolved systems to protect themselves from its effects.
“Studying these fundamental systems is crucial for understanding how radiation can cause cancer, why some people may be more prone to the disease than others and above all how we can kill cancer cells more effectively. This new research is an important advance and we hope it will have real clinical applications.”
The paper is published in Nature421 pp.952-956
By purifying the molecule and studying its size, shape and chemical make-up, researchers were able to link it to a particular gene in the human genome sequence.
Scientists used a new technique called RNA interference to knock out the function of MDC1, in order to study how cells coped with radiation without it.
Prof Jackson’s laboratory was funded by Cancer Research UK. Additional funding for the study came from the Association for International Cancer Research, the A-T Medical Research Trust and the Swiss National Foundation.