Heterochromatin domain number correlates with X-ray and carbon-ion radiation resistance in cancer cells

Radiat Res. 2014 Oct;182(4):408-19. doi: 10.1667/RR13492.1. Epub 2014 Sep 17.

Abstract

Although it is known that cancer cells can develop radiation resistance after repeated exposures to X rays, the underlying mechanisms and characteristics of this radiation-induced resistance of cancer cells are not well understood. Additionally, it is not known whether cells that develop X-ray resistance also would develop resistance to other types of radiation such as heavy-ions including carbon ions (C-ion). In this study, we established X-ray resistant cancer cell lines by delivering repeated exposures to X rays, and then assessed whether the cells were resistant to carbon ions. The mouse squamous cell carcinoma cell line, NR-S1, was X irradiated six times with 10 Gy, and the X-ray resistant cancer cells named X60 and ten subclones were established. Significant X-ray resistance was induced in four of the subclones (X60, X60-H2, X60-A3 and X60-B12). The X60 cells and all of the subclones were resistant to carbon ions. The correlation analysis between radioresistance and morphological characteristics of these cells showed that X-ray (R=0.74) and C-ion (R=0.79) resistance correlated strongly with the number of heterochromatin domains. Moreover, the numbers of γ-H2AX foci remaining in irradiated X60 cells and radioresistant subclones X60-A3 and X60-H2 were lower than in the NR-S1 cells after X-ray or C-ion irradiation, indicating that X60 cells and the radioresistant subclones rapidly repaired the DNA double-strand breaks compared with NR-S1 cells. Our findings suggest that the underlying causal mechanisms of X-ray and C-ion radiation resistance may overlap, and that an increase in heterochromatin domain number may be an indicator of X-ray and C-ion resistance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon / therapeutic use
  • Cell Line, Tumor
  • Heterochromatin / chemistry*
  • Heterochromatin / metabolism*
  • Histones / metabolism
  • Mice
  • Neoplasms / genetics*
  • Neoplasms / pathology*
  • Protein Structure, Tertiary
  • Radiation Tolerance*
  • X-Rays

Substances

  • H2AX protein, mouse
  • Heterochromatin
  • Histones
  • Carbon