Acridine orange (AO) is a known radiation sensitizer, and concomitant local administration of AO and irradiation (5 Gy) after cyto-reductive surgery results in good local control of musculoskeletal sarcomas in humans. Local administration of AO solution into the surgical field can act directly on residual tumor cells, and it is thought that systemic administration of AO may affect tumor cells invading neighboring tissues. However, the toxicity of AO and concomitant X-ray irradiation is not well described. The purpose of the present study was to evaluate the safety of intravenous (IV) administration of AO (1 mg/kg) and simultaneous radiotherapy in mice. To this end, mice were randomly assigned to the following 3 groups (n = 6 in each group): radiotherapy alone (RT alone), IV AO alone (AO alone), and AO and radiotherapy (AO-RT). AO (1 mg/kg) was administered to the AO alone group and the AO-RT group. The mice in the RT alone and AO-RT groups were irradiated with 5 Gy 15 min after injection. The mice were euthanized 72 h after the experiment, and histopathological examinations of the duodenum, jejunum, and ileum were performed. Reductions in crypt proliferative zone and cell division were observed most frequently in the AO alone group, followed by the RT alone and AO-RT groups. Increased apoptotic bodies in crypts and villous atrophy were seen most frequently in the RI alone group, followed by the AO alone and AO-RT groups. Similar results were observed in the jejunum and ileum. However, no significant differences were detected except for reduction of the proliferative zone in the duodenal crypt between the AO-RT and AO alone groups. Histopathological findings of the AO-RT group were not significantly different from those of the RI alone and AO alone groups. Concomitant administration of IV AO (1 mg/kg) and X-ray irradiation appears to be safe for mice.
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