TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible

The objective of this study was to investigate the incidence of overexpression of TP53 (formerly known as p53) in osteosarcomas occurring after treatment of rabbit mandibles with high-dose external-beam radiation. As part of a protocol investigating hyperbaric oxygen treatment for osteoradionecrosis, 102 female New Zealand-White rabbits underwent mandibular radiation treatments with a total dose of 64 Gy in 20 treatment fractions. Twelve animals died during irradiation, leaving 90 animals at risk for tumor development. These animals were divided into one control group and 12 other groups each treated with different schedules of postirradiation hyperbaric oxygen. All animals were sacrificed after the hyperbaric oxygen treatment, approximately 8 months after completion of irradiation. Seventeen of the 90 animals that survived after irradiation developed high-grade osteosarcomas, for a 19% incidence of malignancy. Tumor sizes ranged from 1-4 cm. Immunohistochemistry staining of the 17 tumors detected a 59% overall incidence of TP53 overexpression. There was no correlation between the intensity of hyperbaric oxygen treatment and development of osteosarcoma. The high incidence and short interval of development of osteosarcoma suggest that the study animals may have had a genetic predisposition to radiation-induced osteosarcoma. Additionally, our data provide further evidence that TP53 mutations may play an important role in radiation-induced osteosarcoma.