UPCI, Pitt Researchers Build Mouse Model to Evaluate Compounds to Protect Against Radiation Exposure

4/3/2012

Researchers from the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine have developed a mouse model that will allow scientists to study radiation-induced genetic changes and cellular defense mechanisms against radiation exposure at the same time. The findings will be presented today at the AACR Annual Meeting 2012 in Chicago.

“Often side effects from radiation exposure occur right away, but some take anywhere from six months to two years to manifest. Delayed side effects are caused either by genetic changes from radiation exposure or a breakdown in the body’s cellular defense mechanisms,” said Joel Greenberger, M.D., professor and chairman of the Department of Radiation Oncology at Pitt. “In the past, we haven’t been able to study both causes at the same time. This new mouse model allows us to do that.”

Dr. Greenberger’s team created the model by engineering mice in which activity of the enzyme manganese superoxide dismutase (MnSOD) can be turned on if they are fed or injected with the antibiotic doxycycline. In healthy animals, radiation exposure leads to greater production of toxic free radicals such as superoxides, and in turn MnSOD levels rise to neutralize them. In the engineered mice that do not receive doxycycline, there is no MnSOD activity, and they survive only a few days.

Controlling activation of this enzyme will allow researchers to study the link between two categories of biochemical changes – acute changes caused by immediate radiation exposure and latent reaction that occurs months later. Researchers will be able to examine the antioxidant defense system and better understand molecular events that occur during asymptomatic periods.

This study was sponsored by the National Institute of Allergy and Infectious Diseases, an arm of the National Institutes of Health.