Radiotherapy is an effective method for killing cancer, but the downside is that it harms healthy cells at the same time, sometimes leading to complications. Now researchers from CNIO in Spain have found that boosting levels of a certain protein in the intestines of mice can protect against radiation damage, which could improve the health of cancer patients, victims of nuclear disasters, and future space travellers.
While radiation therapy has helped to boost cancer survival rates over the last few decades, it can cause problems of its own. In patients receiving the treatment for cancers of organs like the liver, pancreas or colon, cells in the intestine can be particularly vulnerable to damage. Although this often heals after the treatment ends, in a few cases it can trigger gastrointestinal syndrome, a lethal condition caused by the death of intestinal cells.
But the body may have a way to defend itself against this condition. In previous work, the CNIO researchers found that high levels of a poorly-understood protein known as URI seemed to protect intestinal cells from DNA damage, caused by radiation exposure.
At least, it worked in cells grown in culture. So the team set out to investigate whether it also applied in the body. To do so, the researchers developed three mouse models with tweaks to the gene that expressed URI in intestinal cells. There was a control group with normal levels of URI, one group that expressed higher levels of the protein and another that had the gene knocked out, in order to lower levels.
After exposing the three groups of mice to high doses of radiation, the team found a clear pattern.
Up to 70 percent of the control group died of gastrointestinal syndrome, while all of the mice with the gene deleted died. But every single mouse that had expressed high levels of URI survived the treatment.
The team also identified the mechanism for how the protein works to protect the cells. URI is expressed in a dormant population of stem cells in the intestinal crypts, and when it's being expressed, those cells aren't proliferating. Since radiation damage only affects cells as they're proliferating, URI is effectively keeping them under the radar.
"However, when URI is not present in these stem cells, the well-known oncogene c-MYC is overexpressed, which leads to cell proliferation and increases susceptibility of these cells to radiation damage," says Almudena Chaves-Pérez, an author of the study. "As a result, these cells die, the intestine does not repair itself, and subsequently, the mouse dies."
Although the study was conducted in mice, the team says that discovering this link could lead to several new treatments in humans. Radiation resistance could be improved by both boosting URI and inhibiting c-MYC, which could reduce the dangerous side effects of radiation and allow for larger doses to be used.
Outside of cancer, the finding could also help other people exposed to radiation. That includes those involved in nuclear disasters or attacks, or astronauts as they venture beyond the Earth's protective atmosphere.
The next steps for the team are to investigate whether stem cell populations in other organs could also be expressing URI.
The research was published in the journal Science.
Source: CNIO
