Anesthetic oxygen use and sex are critical factors in the FLASH sparing effect.

Autor:	Tavakkoli AD; Geisel School of Medicine at Dartmouth., Clark MA; Thayer School of Engineering at Dartmouth., Kheirollah A; Geisel School of Medicine at Dartmouth., Sloop AM; Thayer School of Engineering at Dartmouth., Soderholm HE; Geisel School of Medicine at Dartmouth., Daniel NJ; Thayer School of Engineering at Dartmouth., Petusseau AF; Thayer School of Engineering at Dartmouth., Huang YH; Geisel School of Medicine at Dartmouth., Thomas CR; Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center., Jarvis LA; Department of Radiation Oncology, Dartmouth-Hitchcock Medical Center., Zhang R; Department of Radiation Medicine, New York Medical College., Pogue BW; Department of Medical Physics, University of Wisconsin School of Medicine., Gladstone DJ; Thayer School of Engineering at Dartmouth., Hoopes PJ; Geisel School of Medicine at Dartmouth.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Nov 05. Date of Electronic Publication: 2023 Nov 05.
DOI:	10.1101/2023.11.04.565626
Abstrakt:	Introduction: Ultra-high dose-rate (UHDR) radiation has been reported to spare normal tissue compared to conventional dose-rate (CDR) radiation. However, reproducibility of the FLASH effect remains challenging due to varying dose ranges, radiation beam structure, and in-vivo endpoints. A better understanding of these inconsistencies may shed light on the mechanism of FLASH sparing. Here, we evaluate whether sex and/or use of 100% oxygen as carrier gas during irradiation contribute to the variability of the FLASH effect. Methods: C57BL/6 mice (24 male, 24 female) were anesthetized using isoflurane mixed with either room air or 100% oxygen. Subsequently, the mice received 27 Gy of either 9 MeV electron UHDR or CDR to a 1.6 cm 2 diameter area of the right leg skin using the Mobetron linear accelerator. The primary post-radiation endpoint was time to full thickness skin ulceration. In a separate cohort of mice (4 male, 4 female) skin oxygenation was measured using PdG4 Oxyphor under identical anesthesia conditions. Results: In the UHDR group, time to ulceration was significantly shorter in mice that received 100% oxygen compared to room air, and amongst them female mice ulcerated sooner compared to males. However, no significant difference was observed between male and female UHDR mice that received room air. Oxygen measurements showed significantly higher tissue oxygenation using 100% oxygen as the anesthesia carrier gas compared to room air, and female mice showed higher levels of tissue oxygenation compared to males under 100% oxygen. Conclusion: The FLASH sparing effect is significantly reduced using oxygen during anesthesia compared to room air. The FLASH sparing was significantly lower in female mice compared to males. Both tissue oxygenation and sex are likely sources of variability in UHDR studies. These results suggest an oxygen-based mechanism for FLASH, as well as a key role for sex in the FLASH skin sparing effect.
Databáze:	MEDLINE
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