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Updated: Jan 14, 2026
Ischemic Tissue Injury in the Dorsal Skinfold Chamber of the Mouse: A Skin Flap Model to Investigate Acute Persistent Ischemia
Published on: November 17, 2014
Fractionation increasingly reduces FLASH sparing for acute murine skin damage
Line Kristensen1, Sky Rohrer2, Jacob Graversen Johansen2
1Danish Centre for Particle Therapy, Aarhus University Hospital, Aarhus, Denmark; Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Background And Purpose:
Preclinical studies report a favourable normal tissue-sparing FLASH effect. Most studies report single-fraction irradiations. The interplay between fractionation and FLASH sparing is highly relevant for clinical translation but is scarce in the literature. This study compared the tissue-sparing effect of FLASH on acute skin toxicity with single-fraction, four-fraction and eight-fraction schemes.
Materials And Methods:
Acute skin toxicity after conventional dose rate (CONV, 0.16 Gy/s) and FLASH (mean ± sd 251 ± 12 Gy/s) irradiation was assessed in female CDF1 mice. The right hindleg of unanaesthetised mice was irradiated using a single dose (1 fraction), one daily dose for four consecutive days (4 fractions) or two daily doses with a 6-hour interval for four consecutive days (8 fractions). The study had 4-12 mice per dose group. The total dose per group ranged from 24.5 to 89.9 Gy. A FLASH-enabled accelerator (TrueBeam, Varian) delivered irradiation with a 16 MeV electron beam. Acute skin toxicity was quantified daily from 9 to 28 days post-treatment.
Results:
Single-fraction irradiation had a tissue-sparing FLASH effect, which was halved for four fractions and markedly reduced for eight fractions. The dose modification ratio was 1.41 for a single fraction, 1.18 for four fractions, and nonsignificantly 1.05 for eight fractions.
Conclusion:
Fractionation increasingly reduced the acute skin-sparing effect seen in single-fraction FLASH studies. However, a tissue-sparing effect of 18 % was still present at four fractions, while eight fractions provided a nonsignificant 5 % FLASH skin-sparing. Clinical implementation of FLASH may work best in highly hypofractionated settings.
