Radiological injuries under low energy x-rays in mice depending on dose and protocol: comparative characterization of lesion severity and impact of the in vivo bone response on retrospective dose estimations

Abstract

Abstract Objective. To improve our knowledge about the biological effects of over exposures involving low-energy x-rays, we developed and characterized a preclinical mouse model allowing to mimic different lesion severity degrees induced by 80 kV x-ray depending on the dose and protocol (single or repeated exposure). Approach. Mice were locally exposed (paw) to 80 kV x-rays in a single (15, 30 or 45 Gy in K air) or repeated exposition (2 × 15 or 3 × 15 Gy in K air) to assess different degrees of lesion severity. Six post-irradiation euthanasia time points (0, 7, 14, 21, 42, and 84 days) were determined to follow up the evolution of lesions based on the lesion score, weighing and cutaneous blood perfusion. The bone dose was estimated at the different time points by electron paramagnetic resonance (EPR) spectroscopy. Main results. The monitoring of the lesion severity allows to classify the exposure protocols according to their severity. EPR spectroscopy measurements allow to determine the bone dose on the day of irradiation which is 7 times higher than the initial dose for single protocols. However, the initial signal measured at the end of the repeated exposure was 27% lower than the signal measured for a single dose. The study of the kinetics of EPR signal showed a decrease of the EPR signal which is dependent on the exposure protocol but not on dose highlighting the impact of bone physiology on the bone dose estimation. Significance: the preclinical model developed allows to assess the impact of the dose and protocol on the lesion severity induced by low-energy x-ray. For the first time, the dynamics of free radicals have been quantified in an in vivo model, highlighting that the doses actually administered can be underestimated if samples are taken weeks or even months after exposure.