Radiation-induced growth inhibition in transplanted human tongue carcinomas with different p53 gene status

BACKGROUND AND PURPOSE: To test p53-dependency in radiation cancer therapy with X-rays (low-linear energy transfer (LET)) or carbon-ion (C-) beams (high-LET heavy ion), we analyzed the radiation-induced growth rate and apoptosis induction in human tongue carcinomas transplanted into nude mice. MATERIALS AND METHODS: The SAS cells transfected with mutant p53 gene (SAS/mp53) or a neo control gene (SAS/neo) were transplanted into the thigh of each nude mouse. By measuring the tumor weight (TW), tumor regrowth delay was evaluated when the relative tumor weight (RW) reached 5-fold that of the control group. Apoptosis was analyzed by immunohistochemical and ApopTag stainings. RESULTS: SAS/mp53 tumors were more resistant to X-ray irradiation than SAS/neo tumors, but not to C-beam irradiation. The relative biological effectiveness (RBE) of C-beams compared to X-rays was 2.1 in SAS/neo tumors and 2.6 in SAS/mp53 tumors. Apoptotic cells were more frequently observed in SAS/neo tumors than in SAS/mp53 tumors in X-ray irradiation but not in C-beam irradiation. CONCLUSION: The radiation-induced growth inhibition of transplanted SAS cells is suggested to be p53-dependent in X-ray irradiation but not in C-beam irradiation. C-beams are proposed as being useful for cancer radiation therapy regardless of p53 gene status

p53-dependent hyperthermic enhancement of tumour growth inhibition by X-ray or carbon-ion beam irradiation

To elucidate p53-dependency on combined treatment with radiation and hyperthermia, growth inhibition and apoptosis were analysed using transplantable human tumour. Human head and neck squamous cell carcinoma (HNSCC) cells carrying different p53 genes were transplanted into the thigh of nude mice. When the mean diameter of tumour reached 5-6 mm, the tumours were exposed to X-rays (2 Gy) or Carbon-ion (C-) beams (1 Gy) followed by heating at 42 degrees C for 20 min. Tumour growth inhibition was evaluated by measuring the diameters of tumour. The induction of apoptosis and accumulation of apoptosis-related proteins were also analysed by immunohistochemical staining. Synergistic enhancement of tumour growth inhibition by hyperthermia was observed in wild-type p53 tumours treated with X-rays or C-beams but not in mutant p53 tumours. The incidence of apoptotic cells and activated-caspase-3-positive cells after combined treatment with them were significantly high in wild-type p53 tumours compared with that in mutant p53 tumours. The hyperthermic enhancement of tumour growth inhibition by X-ray- or C-beam-irradiation was p53-dependent, suggesting that it might be highly correlated with p53-dependent apoptosis