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  • Title: High-LET radiation enhanced apoptosis but not necrosis regardless of p53 status.
    Author: Takahashi A, Matsumoto H, Yuki K, Yasumoto J, Kajiwara A, Aoki M, Furusawa Y, Ohnishi K, Ohnishi T.
    Journal: Int J Radiat Oncol Biol Phys; 2004 Oct 01; 60(2):591-7. PubMed ID: 15380596.
    Abstract:
    PURPOSE: We analyzed the death pattern of human lung cancer cells harboring different p53 statuses after irradiation with different levels of linear energy transfer (LET). METHODS AND MATERIALS: We used three kinds of human lung cancer cell lines with identical genotypes, except for the p53 gene. These cells were exposed to X-rays or accelerated carbon-ion beams. The cellular sensitivities were determined by a colony-forming assay. The detection and quantification of cell death (apoptosis and necrosis) were evaluated and compared by acridine orange/ethidium bromide double staining for fluorescence microscopy. RESULTS: We found that (1) there was no significant difference in cellular sensitivity to LET radiation >70 KeV/microm, although wild-type p53 cell sensitivity to X-rays was higher than that of mutated p53 or p53-null cells; (2) low-LET radiation effectively induced apoptosis in wild-type p53 cells as compared with mutated p53 and p53-null cells; and (3) high-LET radiation induced p53-independent apoptosis. CONCLUSIONS: Our findings suggest that high-LET radiotherapy is expected to be a valid application for patients carrying mutated p53 cancer cells. We proposed that the elucidation of the p53-independent apoptosis-related genes might provide new insights into radiotherapy for cancer.
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