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Cancer Gene Radiation Therapy Discovery

September 20, 1999

Dr Tracy Robson, a lecturer in molecular radiation science at the University's Jordanstown campus, has isolated a novel gene, called DIR-1, which can alter a tumour cell's susceptibility to radiation therapy.

Dr Robson and her team were aware that at low doses, normal cells were hypersensitive to radiation: but the patterns of the cells' survival curve indicated that somehow, cells were able to repair damage caused by low doses of radiation.

"I wanted to identify the genes or proteins which were responsible for repairing that radiation damage," said Dr Robson.

And she did.

Advanced molecular techniques enabled her to pull out a gene from a normal cell which was switched off by low dose radiation.

She sequenced the gene, and compared it to the database of known human genes, and found it was a novel gene. She gave it a name: DIR-1 (downregulated ionising radiation-1).

This novel DIR-1 gene was similar to a group of previously identified stress response proteins. These are proteins which are generally activated after a cell has been exposed to various insults - eg radiation, UV light etc.

With further reassert Dr Robson found that if she inhibited DIR-1's action in the cell, the result was faster repair of radiation damage.

"We also looked at tumour cell response to low radiation doses, both in cells known to be sensitive to radiation, and in tumour cells known to be resistant to radiation.

"The results suggested that tumours which were sensitive to radiation do not have the ability to switch on the repair mechanism which normal cells have - and that's why they are amenable to radiation treatment.

"And, conversely, the radiation-resistant tumour cells retain the ability to repair radiation damage: therefore, they must contain the genes or proteins that enable cell repair."

It was the newly-discovered DIR-1 gene which was decisive in protecting cells from radiation damage. And the implications of this discovery or treatments are substantial, said Dr Robson.

"If we switch off this gene, we can protect cells from radiation damage: this could be relevant for people who work in nuclear power plants, labs etc. If, for example there was a nuclear incident like Chernobyl, we could devise and administer a therapy which could help protect affected individuals from further damage e.g. from contaminated food or water or environmental factors.

"On the cancer therapy side if you inhibit DIR 1 and protect cells, that's no good for helping radiation therapy. What can be done instead is to add extra copies of the gene, which would make radiation-resistant tumour cells more sensitive to the effects of radiation, making them more amenable to radiation treatment.

"We would hope to use DIR1 gene therapy for patients whose tumours aren't responding to radiation therapy, making them more receptive to that kind of treatment."

A patent application has been filed on the gene, and the first steps have been made toward commercialising the discovery.

At present, Dr Robinson's team are continuing their work, adding extra copies of the gene to cells at the moment to assess the scale of DIR-1's effect on radiation-resistant tumour cells.

To date, the work has been done using cultured cells: human cell tests are still in the future.

Initially supported by the Cancer Research Campaign, the project has also been supported by Action Cancer NI and Leukaemia Research NI.

ENDS


Ulster, University of