A Murine Combined Injury Model of Total Body Irradiation and Skin Wound

Abstract

In the radiation terrorism scenario there will be combined injuries; we have developed a mouse model of combined injury (total body irradiation (TBI) plus defined skin wound). We measured the effect of TBI doses from 7.0 to 9.25 Gy irradiation on survival and healing of the skin wound. C57BL/6NTac female mice (8 weeks of age) were irradiated to doses of 0 Gy, 7.0 Gy, 8.0 Gy, 8.5 Gy, 9.0 Gy and 9.25 Gy TBI. Twenty-four hours before irradiation, the lower backs were shaved followed by depilation with NAIR. One hour after TBI, mice were anesthetized and a 25 mm length, 5 mm deep scalpel incision/wound was made in the skin. The wound was closed using staples. Control mice received no irradiation and no skin wound. Numbers of surviving mice were recorded daily. At 14, or 20 days after irradiation, groups of control and 0 Gy + wounded mice were sacrificed and wound healing was determined by measuring the tensile strength of each of ten 2 mm strips of skin per mouse across the wound using a 45N capacity tensile tester. On day 28 following irradiation, all remaining mice were tested. The LD50/30 for C57BL/6NTac mice was 9.25 Gy. In the combined injury model the LD50/30 was 8.5 Gy with significantly increased lethality with wounding at 8.5 Gy and 9.0 Gy. Mice irradiated to 9.0 Gy + wound and 8.5 Gy + wound had a statistically significant decrease in survival compared to those receiving 9.0 Gy or 8.5 Gy alone (p = 0.0073 and 0.0115, respectively). The number of deaths in the 8.5 Gy, 9.0 Gy and 9.25 Gy + wound groups was high. We tested the tensile strength in wounds from mice receiving 0 Gy + wound, 7.0 Gy + wound and 8.0 Gy + wound. Compared to the control (non-irradiated, non-wounded) mice tensile strength, the wounds in the combined injury mice were less completely healed at all times. At days 14 and 20, the healing in the 0 Gy + wound was so minimal that we did not measure the other groups until day 28. At 28 days, the mice in the 8.0 Gy + wound group still showed a significantly decreased tensile strength (1.1 ± 0.1 newtons) compared to 1.4 ± 0.1 newtons for the 0 Gy + wound (p = 0.0013). This murine combined injury model of TBI irradiation + wound revealed a clear decreased survival compared to mice receiving TBI only. While longer observation times are needed to monitor the rates of wound healing, mice receiving 8.0 Gy + wound had decreased wound healing compared to 0 Gy + wound.