High linear energy transfer carbon radiation effectively kills cultured glioma cells with either mutant or wild-type p53

Purpose: A mutation in the p53 gene is believed to play an important role i n the radioresistance of many cancer cell lines. We studied cytotoxic effec ts of high linear energy transfer (LET) carbon beams on glioma cell lines w ith either mutant or wild-type p53, Methods and Materials: Cell lines U-87 and U-138 expressing wild-type p53 and U-251 and U-373 expressing mutant pS 3 were used. These cells were irradiated with 290 MeV/u carbon beams genera ted by the Heavy Ion Medical Accelerator in the National Institute of Radio logic Science or X-rays, A standard colony-forming assay and flow cytometri c detection of apoptosis were performed. Cell cycle progression and the exp ression of p53, p21, and bar proteins were examined, Results: High LET carb on radiation was more cytotoxic than low LET X-ray treatment against glioma cells. The effects of the carbon beams were not dependent on the p53 gene status but were reduced by G, arrest, which was independent of p21 expressi on. The expression of bar remained unchanged in all four cell lines. Conclu sion: These results indicate that high LET charged particle radiation can i nduce cell death in glioma cells more effectively than X-rays and that cell death other than p53-dependent apoptosis may participate in the cytotoxici ty of heavy charged particles. Thus, it might prove to be an effective alte rnative radiotherapy for patients with gliomas harboring mutated p53 gene. (C) 2001 Elsevier Science Inc.