Radiation and thermal heat combined exposure invokes early and aggravated multi-organ damage in mice

BACKGROUND: The Hiroshima and Nagasaki bombings raised many unanswered questions about unexpected death caused by combined exposure to radiation and thermal heat. Since then, numerous efforts have been made to understand the complexity of combined radiation and thermal burn exposure, but many gaps remain. This study aimed to analyze the effects of various radiation doses, combined with different thermal burn sizes, on mice. In this study, combined injury (CI) was examined for its effects on mortality, multi-organ damage, changes in body weight and food-water intake, delayed wound healing, and early aging to evaluate early and late consequences across different combinations of radiation dose and burn size. METHOD: C57BL/6 mice were subjected to various radiation doses and different sizes of thermal burns. Animals were monitored for 30 days to evaluate survival, changes in body weight, food and water intake, and hair graying. Changes in organ-to-body weight index (OBWI), vascular permeability assessed by Evans blue extravasation assay, and delayed wound healing were also evaluated to understand acute and subacute effects. RESULTS: Early and higher mortality were observed in animals exposed to CI as the radiation dose and wound size increased. An increase in vital organ OBWI suggested the possibility of interstitial edema in vital organs, which was confirmed through Evans blue extravasation. The same result was evident on the histology slide, too. Radiosensitive organs showed a profound cytotoxic effect after lethal and sublethal combined injury exposure. Early intestinal perforation (day 3) after lethal CI exposure was observed on histology. The order of organ involvement in a CI differs from that in a single stressor, ultimately leading to multi-organ injury. In this study, we also observed early hair graying and delayed wound healing after sublethal CI exposure. OUTCOME: The thermal burn modifies the radiation dose with DMF (Dose Modification Factor) equal to 0.822, thereby exacerbating and accelerating detrimental responses.