Spanish discovery may down radiation side effects

June 5, 2019

Radiotherapy is known to effectively destroy and shrink cancer cells, but will also affect/damage the surrounding healthy cells, leading to toxicity in about 60% of treated patients. For patients with gastrointestinal tumours, intensive radiation therapy could result in gastrointestinal syndrome -characterised by intestinal cell death and ultimately, patient death.

However, data published by Spanish scientists from the Spanish National Cancer Research Centre (CNIO) might prove useful in protecting healthy intestinal cells from high levels of radiation. Their work is based on the URI protein, whose high levels protect mice from radiation-induced intestinal damage, whereas low or no detectable levels of the protein leads to gastrointestinal syndrome.

Nabil Djouder, Head of CNIO’s Growth Factors, Nutrients and Cancer Group has explained that the URI functions similarly to pH or temperature in that its levels must be maintained within a certain range – this determines its reaction to tumour development.

Djouder developed pioneering genetic mouse models to specifically study the protective functions of URI and whether it could mitigate the effects of high-dose irradiations.One mouse model served as a control to identify where URI was expressed in the intestine; another mouse model had high levels of URI expressed in the intestine; while the URI gene was deleted in the third model, subsequently decreasing URI levels in the intestinal epithelium.

In the first model, the control mice showed that URI is expressed in a specific dormant stem cell population located in the intestinal lining, where URI protects against high-dose radiation-induced toxicity by regenerating damaged tissue. With the second model, after being subjected to high-dose radiation, all the mice survived gastrointestinal syndrome as opposed to the estimated 70% fatality rate. Contrastingly, all the mice in the third model died from gastrointestinal syndrome.

The stem cell population expressing URI apparently are not exposed to radiation damage, which only affects proliferating (multiplying) cells. When URI is not present in these stem cells, the well-known oncogene c-MYC is over expressed, which leads to cell proliferation and increased susceptibility to radiation damage. So, these cells die, the intestine does not repair itself, and finally, the mouse dies.

Further research is underway, but Djouder believes that c-MYC inhibitors might reduce lethal side effects of high-dose radiotherapy and protects patients from gastrointestinal syndrome in dual efficacy. The findings have significant implications on cancer research and possibly on cosmic/nuclear radiation.


Category: Features, Health alert

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