Quantified relationship between cellular radiosensitivity, DNA repair defects and chromatin relaxation: a study of 19 human tumour cell lines from different origin.
OBJECTIVE
There is still confusion in the choice of the molecular assays to predict the radiation response of human cells. The case of tumours appears to be particularly complex, may be because of their instability and heterogeneity. The aim of this study was to investigate quantitatively the relationships between DNA double-strand breaks (DSB) repair, chromatin relaxation and cellular radiosensitivity. Nineteen human tumour cell lines, representing a large spectrum of radiation responses and tissues, were examined.


METHODS
Intrinsic radiosensitivity was quantified with surviving fraction at 2 Gy (SF2) as an endpoint. Standard and modified pulsed-field gel electrophoresis techniques were employed to assess DSB repair rate and chromatin relaxation. A cell-free assay was chosen to estimate DSB repair activity, independently of chromatin impairment.


CONCLUSIONS
Surviving fraction at 2 Gy (SF2) decreases linearly with the amount of unrepaired DSB and the extent of chromatin relaxation: one additional unrepaired DSB per cell or 1% chromatin decondensation produce a loss of about 1.5% surviving fraction. However, all the cell lines did not obey both correlations, suggesting that DSB repair and chromatin impairments contribute separately to increase the severity of DNA damage involved in cell lethality. Four cell lines groups showing different DSB repair and/or chromatin impairments were defined. Cell lines exhibiting both DSB repair defect and chromatin relaxation are the most radiosensitive.
Chavaudra
Nicole
N
UPRES EA 2710, Institut Gustave-Roussy, 94805 Villejuif, France.
Bourhis
Jean
J
Foray
Nicolas
N
D015415:Biomarkers / Q000032:analysis; D002470:Cell Survival; D042002:Chromatin Assembly and Disassembly; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D009369:Neoplasms / Q000532:radiotherapy; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
D015415:Biomarkers