Effect of heavy ion beams on intratumoral radioresistant tumor cells

The purpose of this study is to investigate the radiobiological effect of heavy ion beams on radioresistant and radiosensitive human tumor cells. Tumors of human origin, an ependymoblastoma (EB) with wild-type (wt) p53, a primitive neuroectodermal tumor (PNET) with wt p53, and a glioblastoma (GB) with mutant-type (mt) p53, were transplanted to nude mice, and the mice were irradiated with carbon ion beams (290 MeV/u) or 200 kV X-rays. Tumors were excised 4, 6, or 24 hours after 2 Gy irradiation. A part of each tumor was fixed in formalin and embedded in paraffin. Thin sections were stained with H.E., GFAP or TUNEL for microscopic study. Total RNA was extracted for cDNA microarray analysis. In wt-p53 tumors, apoptosis increased 4 or 6 hours after irradiation. The tumors with wt-p53 showed significant changes in gene expression following 2 Gy irradiation. Pathway analysis of up- and down-regulated genes demonstrated that apoptosis, p53 signaling pathway, and cell cycle are involved significantly. There was little difference between the gene expression profiles induced by carbon ion beams and those by X-rays. In contrast, the tumor with mt-p53 showed much less change in gene expression after 2 Gy irradiation. But, the tumor showed significant changes 4, 6, or 24 hours after 8 Gy or 16 Gy irradiation, 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. (author)