Comparison of Gonadal Toxicity of Single-Fraction Ultra-High Dose Rate and Conventional Radiation in Mice
Maria C. Cuitiño, Jessica L. Fleming, Sagarika Jain, Ashley J. Cetnar, Ahmet S. Ayan, J Woollard, Heather R. Manring, Wei Meng, Joseph P. McElroy, Dukagjin Blakaj, Nilendu Gupta, Arnab Chakravarti
Abstract
Purpose Increasing evidence suggests that ultra-high dose rate (UHDR) radiation could result in similar tumor control as conventional (CONV) radiotherapy (RT) while reducing toxicity to surrounding healthy tissues. Considering that radiation toxicity to gonadal tissues can cause hormone disturbances and infertility in young cancer patients, the purpose of this study was to assess the possible role of UHDR-RT in reducing toxicity to healthy gonads in mice as compared to CONV-RT. Methods and Materials Radiation was delivered to the abdomen or pelvis of female (8 or 16 Gy) and male (5 Gy) C57BL6 mice, respectively, at conventional (∼0.4 Gy/s) or ultrahigh (>100 Gy/s) dose rates using an IntraOp Mobetron linear accelerator. Organ weights along with histopathology and immunostaining of irradiated gonads were used to compare toxicity between radiation modalities. Results CONV- and UHDR-RT induced a similar decrease in uterine weights at both studied doses (∼50% of controls), which indicated similarly reduced ovarian follicular activity. Histologically, ovaries of CONV- and UHDR-irradiated mice exhibited a comparable lack of follicles. Weights of CONV- and UHDR-irradiated testes were reduced to ∼30% of controls, and the percent of degenerate seminiferous tubules was also similar between radiation modalities (∼80% of controls). Pairwise comparisons of all quantitative data indicated statistical significance between irradiated (CONV or UHDR) and control groups (from P ≤ 0.01 to P ≤ 0.0001) but not between radiation modalities. Conclusions The data presented here suggest that the short-term effects of UHDR-RT on the mouse gonads are comparable to those of CONV-RT.