Drosophila helps to elucidate the effects of radiation therapy

Children who are exposed to cranial radiation therapy (CRT) to treat brain tumours are at increased risk later in life for neurocognitive, motor and seizure disorders. Current radioprotective agents are difficult to administer and have severe side effects. Thus, Barry Ganetzky and colleagues used Drosophila to model and elucidate the toxic effects of CRT during juvenile development. First, they found that irradiating fly larvae with different doses of radiation reduces the percentage of animals that survive to adulthood and impairs motor activity of surviving adults, in a dose-dependent manner. These phenotypes are paralleled by an increased expression of activated death caspase-1, a cell death marker, in adult brains. Then, using flies at different developmental stages, they found that the toxic effects of radiation exposure become more severe with decreasing larval age at time of irradiation. Notably, flies with different genetic backgrounds show different sensitivity to radiation. Thus, Drosophila represents a useful system to model CRT-induced toxicity and to dissect key molecular and genetic pathways. These, in turn, might illuminate potential targets for radioprotective purposes. Page 669