Combined injury: irradiation with skin or bone wounds in rodent models

Abstract

A radiation combined injury is defined as an injury that occurs in the setting of irradiation, such as those expected after a nuclear accident, radiation dispersal device release (a 'dirty bomb'), or a nuclear weapon detonation. There is much research on irradiation-associated burns and their healing, but there is less known about other injuries sustained in the context of irradiation. Animal models are limited in their correlations to clinical situations but can support research on specific questions about injuries and their healing. Mouse models of irradiation with skin or bone wounds are validated as highly reproducible and quantitative. They show dose-dependent impairment of wound healing, with later recovery. Irradiation-induced delay of bone wound healing was mitigated to different extents by single doses of gramicidin S-nitroxide JP4-039, a plasmid expressing manganese superoxide dismutase, amifostine/WR2721, or the bifunctional sulfoxide MMS-350. These models should be useful for research on mechanisms of radiation dermal and osseous damage and for further development of new radioprotectors. They also provide information of potential relevance to the effects of clinical radiation therapies.

Keywords: animal models; bone wound; healing; radiation combined injury (RCI); skin wound.

Figure 1.

Effect of local irradiation dose on skin wound healing. Tensile strengths (Newtons) were measured and expressed as the mean ± s.e.m. for each group of skin strips from seven mice. p values were calculated for each group against intact skin.

Figure 2.

Effects of incisional skin wound on survival of mice following TBI. p values were calculated comparing data with and without skin wounds for each radiation dose (n = 7 per group).

Figure 3.

Effect of irradiation dose on incisional wound healing at day 28. Mean values for groups of 12 mice are shown.

Figure 4.

Effects of genotype (NOD/SCID, C57BL/6NHsd, SAMP6, SAMR1) and local 20 Gy irradiation on % of bone wound healed on day 21. Asterisks indicate statistically significant differences between 0 and 20 Gy. Data are adapted from [23].

Figure 5.

Effects of irradiation dose to the leg on healing of tibial osseous wounds, as evaluated by measurement of hole diameter on radiographs. Upper panels show radiographs of selected control mice (0 Gy). The lower panel shows rates of closure/healing of wounds from groups of 5 mice. The dotted line represents time course for the control group. *Asterisks indicate statistically significant differences between the irradiated group and control group. Data is adapted from [22].

Figure 6.

Effects of agents on irradiation-induced delay of bone wound healing. (A) All groups received 20 Gy to the leg. (B) All groups received 20 Gy to the leg. Agents were given 24h before or after irradiation. (C), (D) Mice whose legs were or were not irradiated were treated with MMS-350 or vehicles; wounds were measured by radiography (C) or by micro-CT (D). *Asterisks indicate statistical significance. Data for (A) and (B) is adapted from [22].