TP53 overexpression in radiation-induced osteosarcoma of the rabbit mandible

The objective of this study was to investigate the incidence of overexpress ion of TP53 (formerly known as p53) in osteosarcomas occurring after treatm ent 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 treat ments 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 animal were divided into one control group and 12 other groups each t reated with different schedules of postirradiation hyperbaric oxygen. All a nimals 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% i ncidence of malignancy. Tumor sizes ranged from 1-4 cm, Immunohistochemistr y staining of the 17 tumors detected a 59% overall incidence of TP53 overex pression. There was no correlation between the intensity of hyperbaric oxyg en 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, Additi onally, our data pro,ide further evidence that TP53 mutations may play an i mportant role in radiation-induced osteosarcoma. (C) 1999 by Radiation Rese arch Society.