Under the auspices of the National Aeronautics and Space Administration (NASA), we are studying cellular responses to complex DNA damage inflicted by the HZE (High-Z, High-Energy) component of galactic cosmic rays.
We find that mammalian cells are unable to repair a significant portion of DSBs induced by HZE particles and, as a consequence, these ions are highly transforming compared to gamma or X-rays. We are currently examining HZE-induced gliomagenesis in compound transgenic mouse models with brain-restricted tumor suppressor deletions. We find that loss of the Ink4a/b-Rb and Arf-p53 tumor suppressor axes and amplification of the MET and PDGFR proto-oncogenes are critical events in the transformation process.
Our research on HZE particles is very pertinent to NASA as the decision to launch future long-duration space missions hinges upon the accurate estimation of cancer risks to astronauts from these particles. Moreover, this research is also very relevant to cancer therapy due to the increasing use of charged particles (protons and carbon) for targeted tumor therapy in the clinic.