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

Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):591-7. doi: 10.1016/j.ijrobp.2004.05.062.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Apoptosis / radiation effects*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / radiotherapy
  • Cell Survival / radiation effects
  • Genes, p53*
  • Humans
  • Linear Energy Transfer*
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / radiotherapy*
  • Necrosis
  • Radiation Tolerance / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured / radiation effects
  • Tumor Stem Cell Assay