Deciphering Ultra-High Dose Rate Irradiation with Drosophila melanogaster

Area of Science:

• Radiation oncology
• Preclinical research
• Model organism studies

Background:

• Ultra-high dose rate (UHDR) radiation, known as FLASH radiotherapy (RT), shows promise for reducing normal tissue damage while preserving tumor control.
• Clinical translation of FLASH RT requires a deeper mechanistic understanding, necessitating new in vivo models for research.

Purpose of the Study:

• To investigate the differential biological effects of UHDR and conventional (CONV) irradiation using the fruit fly model.
• To evaluate the potential of *D. melanogaster* as a preclinical model for mechanistic studies of FLASH RT.

Main Methods:

• Adult female *D. melanogaster* were irradiated with electron beams (16 MeV and 9 MeV) at UHDR (3000-7000 Gy/s) and CONV (0.5 Gy/s) dose rates.
• Lifespan, climbing ability, and lipid peroxidation levels (indicating ferroptosis) were assessed as biological endpoints.

Main Results:

• UHDR irradiation led to substantial lifespan prolongation compared to CONV irradiation, particularly at high doses (1000-1500 Gy).
• Split-dose UHDR irradiation further enhanced lifespan compared to single high-dose UHDR.
• CONV irradiation induced climbing deficits and ferroptosis in fly brains, effects not observed with single high-dose UHDR irradiation.

Conclusions:

• *D. melanogaster* exhibits differential responses to UHDR and CONV irradiation, highlighting its utility as a practical preclinical model.
• The fruit fly model can be used to mechanistically investigate the protective effects of FLASH RT against radiation-induced damage.