Abstract
Cell death induced by radiation therapy for patients in clinic is not as clear as in vitro study. p53-dependent apoptosis is frequently induced by radiation in radiosensitive tumor and normal cells in vivo; however, few apoptotic cell deaths are found in the majority of tumor and normal cells in vivo following irradiation. To investigate low LET X-ray- and high LET beam-induced cell death and gene expression profiles in human tumors with different p53 status, an ependymoblastoma with wild-type p53, a primitive neuroectodermal tumor with wild-type p53, and a glioblastoma with mutant-type p53, were transplanted into nude mice subcutaneously, and irradiated with 200kV X-rays or carbon ion beams (290MeV/u, 6 cm spread-out Bragg peak, NIRS). These tumors were excised 4, 6, or 24 hours (h) after 2Gy irradiation. Additionally, glioblastoma was examined 6 h after 8 or 16Gy irradiation. Total RNA was extracted for GeneChip expression microarray analysis. Hierarchical clustering, gene ontology analysis, and pathway analysis were also performed. Tumors with wild-type p53 showed significant changes in gene expression following 2Gy irradiation and most profiles by carbon ion and X-rays were similar. Glioblastoma with mutant-type p53 showed little change after 2Gy; however, significant changes in gene expression were induced by 8Gy or 16Gy, and the gene expression profiles induced by carbon ion beams were different from those by X-rays. p53, caspases, Fas, and TRAIL were not involved in the pathways, but NF-kB and IAP were suggested to be involved.
