High-LET radiation enhanced apoptosis but not necrosis regardless of p53 status

Abstract

<h3>Purpose</h3> We analyzed the death pattern of human lung cancer cells harboring different <i>p53</i> statuses after irradiation with different levels of linear energy transfer (LET). <h3>Methods and materials</h3> We used three kinds of human lung cancer cell lines with identical genotypes, except for the <i>p53</i> 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. <h3>Results</h3> We found that <i>(1)</i> there was no significant difference in cellular sensitivity to LET radiation >70 KeV/μm, although wild-type <i>p53</i> cell sensitivity to X-rays was higher than that of mutated <i>p53</i> or <i>p53</i>-null cells; <i>(2)</i> low-LET radiation effectively induced apoptosis in wild-type <i>p53</i> cells as compared with mutated <i>p53</i> and <i>p53</i>-null cells; and <i>(3)</i> high-LET radiation induced <i>p53</i>-independent apoptosis. <h3>Conclusions</h3> Our findings suggest that high-LET radiotherapy is expected to be a valid application for patients carrying mutated <i>p53</i> cancer cells. We proposed that the elucidation of the <i>p53</i>-independent apoptosis-related genes might provide new insights into radiotherapy for cancer.