title: Heterochromatin domain number correlates with X-ray and carbon-ion radiation resistance in cancer cells.
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.
authors.affiliation: a  Cancer Metastasis Research Team.
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Imai
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Okayasu
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D002244:Carbon / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D017434:Protein Structure, Tertiary; D011836:Radiation Tolerance; D014965:X-Rays
chemical_list: D002244:Carbon; D006570:Heterochromatin; D006657:Histones; C475961:gamma-H2AX protein, mouse