The Role of Oxygen in the Skin-Sparing Effect of Flash Proton Irradiation

Abstract

Ultra-high dose rate irradiation (Flash irradiation) has been proved to be able to spare normal tissues. Radiation-induced oxygen depletion might contribute to the effect. In the present study, we try to verify the protective effect of Flash proton irradiation on the skin and highlight the association of oxygen with it.A Flash proton experimental platform utilizing a 228.9 MeV proton beam was established to generate a homogenous field of 1.2Í1.6 cm2. Physical dosimetry and biological experiments with normal air condition cultured cells were conducted to affirm the dose. Two biologically independent experiments were conducted at the doses of 25 Gy and 27 Gy respectively. The skin tattoos were made by intracutaneously injected Indian ink to help to detect the contraction fraction. The mice of the Flash+O2 cohort were kept inside a designed chamber from 6 minutes before irradiation to the end of the exposure. Tying the legs of the hypoxic cohorts for 3 minutes helped to generate an anoxic skin condition. The epidermis thickness of the 25 Gy irradiated mice was measured with the hematoxylin-eosin-stained slides.Compared with the 27 Gy conventional dose rate (CDR) irradiated group, the same dose of Flash proton irradiation led to less skin contraction. The contraction fraction of the Flash irradiated oxygen-breathing group was similar to that of the normal CDR group but was significantly different from the Flash group. No difference was detected between the hypoxic 27 Gy Flash and CDR cohorts. The skin contraction fractions of each cohort at 72 days after irradiation were showed in Table 1. An essentially identical Flash effect was obtained at 25 Gy (P = 0.0073, Flash vs CDR). The epidermis thickness of the Flash group was comparable to the control group, whereas the CDR irradiation caused epidermal incrassation.Flash proton irradiation decreased the skin contraction and epidermis thickness of mice. This effect is related to oxygen depletion during the irradiation procedure. Table 1. Skin contraction fractions at 72 days after irradiation (x̄ ± SD).