The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, UMR9020-U1277 - CANTHER - Cancer Heterogeneity, Plasticity and Resistance to Therapies, France
- Univ. Lille, CNRS, UMR8520, Institut d'Electronique, Microélectronique et Nanotechnologie, France
- Oncovet Clinical Research, Plateforme PRECI, France
- Oncovet, Plateforme PRECI, France
- Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - CIIL - Centre d'Infection et d'Immunité de Lille, France
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011 - EGID, France
- Lille University, Medical School and Centre Oscar Lambret, France
Figures
Figure 1 with 4 supplements
Growth curves and cell death level of MDA-MB231 and normal human dermal fibroblasts (NHDFs) positioned at the margin or inside a planning target volume (PTV) receiving 2 Gy/day.
(A) Growth curves of MDA-MB231 positioned inside the PTV and irradiated or not during 3 weeks. (B) Growth curves of NHDFs (donor F6MC1, population doubling [PD] = 30.36 at the beginning of the …
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Figure 1—source data 1
Data for growth curves of MDA-MB231.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-data1-v1.xlsx
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Figure 1—source data 2
Data for growth curves of normal human dermal fibroblasts (NHDFs).
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-data2-v1.xlsx
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Figure 1—source data 3
Data for cell death assays of normal human dermal fibroblasts (NHDFs) and MDA-MB231.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-data3-v1.xlsx
Figure 1—figure supplement 1
Physical parameters of the linear accelerator (Varian Primus CLINAC).
(A) Image of the Varian Primus CLINAC used in the study (except experiments on mice). (B) Varian Primus CLINAC’s depth profile recorded in photon mode at 6 or 20 MV.
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Figure 1—figure supplement 1—source data 1
Data for the depth profile.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-figsupp1-data1-v1.xlsx
Figure 1—figure supplement 2
Cell irradiation setup.
(A) Schematic representation of how 96-, 12-, or 6-well plates were irradiated. Plates were put on a 2- or 4-cm-thick poly(methyl methacrylate) (PMMA) plate laid on the carbon fiber table for an …
Figure 1—figure supplement 3
Growth curves of normal human dermal fibroblasts (NHDFs) from another donor positioned at the margin or inside a planning target volume (PTV) receiving 2 Gy/day.
Growth curves of NHDFs (donor F1MC1, population doubling [PD] = 26.3 at the beginning of the experiment) cultured in 6-well plates irradiated at 2 Gy/day except weekends during 3 weeks. The days of …
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Figure 1—figure supplement 3—source data 1
Data for growth curves.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-figsupp3-data1-v1.xlsx
Figure 1—figure supplement 4
Cell death level of normal human dermal fibroblasts (NHDFs) from two other donors positioned at the margin or inside a planning target volume (PTV) receiving 2 Gy/day.
(A) MDA-MB231 cultured in 100 mm dishes were irradiated or not at 2 Gy/day except weekends up to six irradiations. The dishes were entirely located inside the PTV. NHDFs (A: donor F1MC1, population …
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Figure 1—figure supplement 4—source data 1
Data for Alexa Fluor 488 Annexin Dead Cell Apoptosis assays.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-figsupp4-data1-v1.xlsx
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Figure 1—figure supplement 4—source data 2
Data for Annexin V-positive cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig1-figsupp4-data2-v1.xlsx
Figure 2 with 5 supplements
Normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day undergo senescence.
Six-well plates of NHDFs (donor F1MC1, population doubling [PD] = 25.8 at the beginning of the experiment) positioned straddling the PTV and the margin were irradiated during 3 weeks at 2 Gy/day …
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Figure 2—source data 1
Data for SA-β-Gal activity.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-data1-v1.xlsx
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Figure 2—source data 2
Data for forward scatter (FSC) and side scatter (SSC levels).
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-data2-v1.xlsx
Figure 2—figure supplement 1
Normal human dermal fibroblasts (NHDFs) from another donor positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day undergo senescence.
NHDFs (donor F6MC1, population doubling [PD] = 32.4 at the beginning of the experiment) cultured in 12-well plates were irradiated or not at 2 Gy each day except weekends for a total of 10 radiation …
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Figure 2—figure supplement 1—source data 1
Values of C12FDG fluorescence intensity.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp1-data1-v1.xlsx
Figure 2—figure supplement 2
Normal human dermal fibroblasts (NHDFs) positioned at the margin of the planning target volume (PTV) receiving 2 Gy/day become cell cycle arrested in G1.
NHDFs (donor F1MC1, population doubling [PD] = 25.8 at the beginning of the experiment) cultured in 6-well plates were irradiated or not at 2 Gy/day except weekends up to 13 times. NHDFs at …
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Figure 2—figure supplement 2—source data 1
Quantification of cells in the different phases of the cell cycle.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp2-data1-v1.xls
Figure 2—figure supplement 3
Induction of p16 and p21 expression in normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day.
NHDFs (donor F6MC1, population doubling [PD] = 18 at the beginning of the experiment) cultured in 12-well plates were irradiated or not at 2 Gy/day except weekends for different durations (2 × 2 Gy, …
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Figure 2—figure supplement 3—source data 1
RT-qPCR data for p16.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp3-data1-v1.xlsx
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Figure 2—figure supplement 3—source data 2
RT-qPCR data for p21.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp3-data2-v1.xlsx
Figure 2—figure supplement 4
Induction of p16 in normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day.
NHDFs (donor F6MC1, population doubling [PD] = 18 at the beginning of the experiment) cultured in 12-well plates were irradiated or not at 2 Gy/day except weekends for different durations (1 × 2 Gy, …
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Figure 2—figure supplement 4—source data 1
Western blot of p16.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp4-data1-v1.pptx
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Figure 2—figure supplement 4—source data 2
Quantification of p16-positive cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp4-data2-v1.xlsx
Figure 2—figure supplement 5
A significant proportion of normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day become multinucleated.
Three independent series of fluorescent microscopy images from three immunofluorescence experiments were reanalyzed for the presence of multinucleated cells. In these experiments, NHDFs were …
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Figure 2—figure supplement 5—source data 1
Quantification of multinucleated cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig2-figsupp5-data1-v1.xlsx
Figure 3 with 6 supplements
Single-strand breaks (SSBs) and double-strand breaks (DSBs) generated in normal human dermal fibroblasts (NHDFs) positioned at the margin or inside a planning target volume (PTV) having received 2 Gy.
(A) Proliferating NHDFs (donor F1MC1, population doubling [PD] = 32) positioned straddling the PTV and the margin were irradiated once at 2 Gy. Cells were fixed 20 min or 2 hr later for the …
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Figure 3—source data 1
Number of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data1-v1.xlsx
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Figure 3—source data 2
Number of 53BP1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data2-v1.xlsx
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Figure 3—source data 3
Statistics on comet assays at pH 12.3.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data3-v1.pdf
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Figure 3—source data 4
Comet assays at pH 12.3.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data4-v1.xlsx
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Figure 3—source data 5
Comet assays at pH 8.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data5-v1.xlsx
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Figure 3—source data 6
Statistics on comet assays at pH 8.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-data6-v1.pdf
Figure 3—figure supplement 1
Representative images of XRCC1 and 53BP1 foci recorded by high-content microscopy.
Proliferating normal human dermal fibroblasts (NHDFs) (donor F1MC1, population doubling [PD] = 32) cultured in 96-well plates positioned straddling the planning target volume (PTV) and the margin …
Figure 3—figure supplement 2
Normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy do not suffer from double-strand breaks (DSBs).
Proliferating NHDFs (donor F6MC1) cultured in 6-well plates positioned straddling the PTV were irradiated once at 2 Gy. Cells were fixed 2 hr later for the immunodetection of γH2AX and 53BP1, …
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Figure 3—figure supplement 2—source data 1
Quantification of γH2AX foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp2-data1-v1.xlsx
Figure 3—figure supplement 3
Single-strand breaks (SSBs) and double-strand breaks (DSBs) generated in normal human dermal fibroblasts (NHDFs) derived from different donors positioned at the margin or inside a planning target volume (PTV) receiving 2 Gy.
Proliferating NHDFs (F26MC1, population doubling [PD] = 6.2; F1MC1, PD = 24.3) cultured in 12-well plates were irradiated at 2 Gy and then processed for comet assays as in Figure 3B. About 100 cells …
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Figure 3—figure supplement 3—source data 1
Comet assays at pH 12.3 with F26MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data1-v1.xlsx
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Figure 3—figure supplement 3—source data 2
Statistics on comet assays at pH 12.3 with F26MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data2-v1.pdf
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Figure 3—figure supplement 3—source data 3
Comet assays at pH 8 with F26MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data3-v1.xlsx
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Figure 3—figure supplement 3—source data 4
Statistics on comet assays at pH 8 with F26MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data4-v1.pdf
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Figure 3—figure supplement 3—source data 5
Comet assays at pH 12.3 with F1MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data5-v1.xlsx
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Figure 3—figure supplement 3—source data 6
Statistics on comet assays at pH 12.3 with F1MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data6-v1.pdf
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Figure 3—figure supplement 3—source data 7
Comet assays at pH 8 with F1MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data7-v1.xlsx
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Figure 3—figure supplement 3—source data 8
Statistics on comet assays at pH 8 with F1MC1 NHDFs.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp3-data8-v1.pdf
Figure 3—figure supplement 4
The numbers of 53BP1 and XRCC1 foci recorded after an irradiation with 6 and 20 MV photon beams are similar.
Proliferating normal human dermal fibroblasts (NHDFs) (donor F1MC1, population doubling [PD] = 39) cultured in 96-well plates were irradiated as in Figure 3 at 2 Gy by a photon beam of 6 or 20 MV. …
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Figure 3—figure supplement 4—source data 1
Number of XRCC1 and 53BP foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp4-data1-v1.xlsx
Figure 3—figure supplement 5
A propagation of ionizing particles in the material is necessary for single-strand break (SSB) induction at distance from the planning target volume (PTV).
(A) Schematic representation of how the 12-well plates were aligned, sealed or not together with an ultrasound gel (250820, Asept Inmed), in order to have wells inside the PTV and wells in the …
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Figure 3—figure supplement 5—source data 1
Number of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp5-data1-v1.xlsx
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Figure 3—figure supplement 5—source data 2
Statistics on XRCC1 foci number.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp5-data2-v1.pdf
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Figure 3—figure supplement 5—source data 3
Number of 53BP1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp5-data3-v1.xlsx
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Figure 3—figure supplement 5—source data 4
Statistics on 53BP1 foci number.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp5-data4-v1.pdf
Figure 3—figure supplement 6
The proliferating versus quiescent status of normal human dermal fibroblasts (NHDFs) does not interfere with the generation of single-strand breaks (SSBs).
NHDFs’ (F6MC1, population doubling [PD] = 27.8) proliferation was slowed down by starvation in 0.1% fetal bovine serum (FBS) instead of the normal 2% FBS concentration. (A) Cell cycle analysis …
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Figure 3—figure supplement 6—source data 1
Quantification of cells in the different phases of the cell cycle.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp6-data1-v1.xlsx
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Figure 3—figure supplement 6—source data 2
Comet assays.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig3-figsupp6-data2-v1.xlsx
Figure 4 with 1 supplement
Mice positioned at the margin of a phantom mimicking a planning target volume (PTV) irradiated once at 2 Gy have a significant increase of XRCC1 foci.
(A) Schematic representation of how mice were positioned at the margin of a phantom. (B) Six mice (three females and three males) were irradiated as in (A), one mouse was irradiated positioned …
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Figure 4—source data 1
Number of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-data1-v1.xlsx
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Figure 4—source data 2
Statistics on XRCC1 foci numbers.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-data2-v1.pdf
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Figure 4—source data 3
Number of 53BP1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-data3-v1.xlsx
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Figure 4—source data 4
Statistics on 53BP1 foci numbers.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-data4-v1.pdf
Figure 4—figure supplement 1
Mice positioned at the margin of a phantom mimicking a planning target volume (PTV) irradiated once at 2 Gy have a significant increase of XRCC1 foci in dermal fibroblasts.
(A) Mice irradiated as in Figure 4 were sacrificed 1 hr after irradiation. Skin samples at different distances from the isodose 50 (the spine), established as the zero, were dissected and …
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Figure 4—figure supplement 1—source data 1
Quantification of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-figsupp1-data1-v1.xlsx
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Figure 4—figure supplement 1—source data 2
Statistics on the quantification of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig4-figsupp1-data2-v1.pdf
Figure 5 with 3 supplements
Single-strand breaks (SSBs) accumulate with successive irradiations in normal human dermal fibroblasts (NHDFs) positioned at the margin of a planning target volume (PTV) receiving 2 Gy/day.
Proliferating NHDFs (donor F6MC1, population doubling [PD] = 22.67) cultured in 12-well plates were irradiated or not only one time at 2 Gy or during 5 days at 2 Gy daily. Just after the last …
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Figure 5—source data 1
Comet assays at pH 8 for the planning target volume (PTV).
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data1-v1.xlsx
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Figure 5—source data 2
Statistics on comet assays at pH 8.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data2-v1.pdf
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Figure 5—source data 3
Statistics on comet assays at pH 12.3.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data3-v1.pdf
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Figure 5—source data 4
Comet assays at pH 8 for the margin –5 + 20.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data4-v1.xlsx
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Figure 5—source data 5
Comet assays at pH 8 for the margin +22 + 47.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data5-v1.xlsx
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Figure 5—source data 6
Comet assays at pH 12.3 for the planning target volume (PTV).
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data6-v1.xlsx
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Figure 5—source data 7
Comet assays at pH 12.3 for the margin –5 + 20.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data7-v1.xlsx
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Figure 5—source data 8
Comet assays for the margin +22 + 47.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-data8-v1.xlsx
Figure 5—figure supplement 1
Single-strand breaks (SSBs) generated in normal human dermal fibroblasts (NHDFs) positioned at the margin of the planning target volume (PTV) are no more repaired after five successive irradiations at 2 Gy.
Proliferating NHDFs (F6MC1, population doubling [PD] = 20.3 at the beginning of the experiment) cultured in 12-well plates were irradiated at 2 Gy/day for 1 (1 × 2 Gy) or 5 days (5 × 2 Gy). After …
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Figure 5—figure supplement 1—source data 1
Comet assays pH 12.3.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp1-data1-v1.xlsx
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Figure 5—figure supplement 1—source data 2
Statistics on comet assays pH 12.3.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp1-data2-v1.pdf
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Figure 5—figure supplement 1—source data 3
Comet assays pH 8.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp1-data3-v1.xlsx
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Figure 5—figure supplement 1—source data 4
Statitstics on comet assays pH 8.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp1-data4-v1.pdf
Figure 5—figure supplement 2
The repair of single-strand breaks (SSBs) generated in normal human dermal fibroblasts (NHDFs) positioned at the margin of the planning target volume (PTV) becomes poorly efficient after four successive irradiations at 2 Gy.
Proliferating NHDFs (F6MC1, population doubling [PD] = 19) cultured in 96-well plates were irradiated at 2 Gy/day for 4 days (4 × 2 Gy). Then, they were fixed at indicated time and an …
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Figure 5—figure supplement 2—source data 1
Quantification of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp2-data1-v1.xlsx
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Figure 5—figure supplement 2—source data 2
Quantification of 53BP1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp2-data2-v1.xlsx
Figure 5—figure supplement 3
The PARylation capacity decreases with successive irradiations.
(A) Analysis of the PARylation capacity in normal human dermal fibroblasts (NHDFs) (F6MC1, population doubling [PD] = 32.4 at the beginning of the experiment) positioned at the margin or inside a …
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Figure 5—figure supplement 3—source data 1
Quantification of PAR foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp3-data1-v1.xlsx
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Figure 5—figure supplement 3—source data 2
Statistics on quantification of PAR foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig5-figsupp3-data2-v1.pdf
Figure 6 with 2 supplements
Some radio-induced senescent cells generated in the margin escape from senescence to generate a progeny of cells that reproliferate, have an increased invasion capacity, and display mutations.
(A) Normal human dermal fibroblasts (NHDFs) (donor F6MC1, population doubling [PD] = 29.6 at the beginning of the experiment) positioned straddling the planning target volume (PTV) and the margin …
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Figure 6—source data 1
Data of growth curves.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-data1-v1.xlsx
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Figure 6—source data 2
Quantification of 6-thioguanine (6-TG)-resistant cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-data2-v1.xlsx
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Figure 6—source data 3
Zymography.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-data3-v1.pptx
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Figure 6—source data 4
Quantification of cell migration and invasion.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-data4-v1.xlsx
Figure 6—figure supplement 1
Principle of senescent cell sorting.
Figure 6—figure supplement 2
Similar experiment as in Figure 6 with normal human dermal fibroblasts (NHDFs) derived from another donor.
(A) NHDFs (donor F1MC1, population doubling [PD] = 26.83 at the beginning of the experiment) cultured in 6-well plates were irradiated or not at 2 Gy/day except weekends during 2 weeks. Cells were …
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Figure 6—figure supplement 2—source data 1
Growth curves.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-figsupp2-data1-v1.xlsx
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Figure 6—figure supplement 2—source data 2
Quantification of 6-thioguanine (6-TG)-resistant cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig6-figsupp2-data2-v1.xlsx
Figure 7 with 4 supplements
A single-strand break (SSB) accumulation is enough to induce senescence and post-senescence neoplastic escape (PSNE).
(A) Analysis of XRCC1 foci by immunofluorescence in normal human dermal fibroblasts (NHDFs) (F1MC1, population doubling [PD] = 44.07 at the beginning of the experiment) treated daily or not with …
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Figure 7—source data 1
Number of XRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-data1-v1.xlsx
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Figure 7—source data 2
Quantification of SA-β-Gal assays.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-data2-v1.xlsx
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Figure 7—source data 3
Growth curves.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-data3-v1.xlsx
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Figure 7—source data 4
Quantification of 6-thioguanine (6-TG)-resistant cells.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-data4-v1.xlsx
Figure 7—figure supplement 1
The combined poly(ADP)ribose polymerase (PARP) inhibitor + H2O2 treatment does not induce other oxidative damages than single-strand breaks (SSBs).
(A) PARylation synthesis assay in normal human dermal fibroblasts (NHDFs) (F1MC1, population doubling [PD] = 46) treated during 24 hr with different concentrations of veliparib and challenged for 10 …
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Figure 7—figure supplement 1—source data 1
Western-blots.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp1-data1-v1.pptx
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Figure 7—figure supplement 1—source data 2
Quantification of 53BP1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp1-data2-v1.xlsx
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Figure 7—figure supplement 1—source data 3
Quantification of hOGG1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp1-data3-v1.xlsx
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Figure 7—figure supplement 1—source data 4
Quantification of red on green fluorescence.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp1-data4-v1.xlsx
Figure 7—figure supplement 2
The repair of single-strand breaks (SSBs) is blocked during a veliparib + H2O2 treatment.
Normal human dermal fibroblasts (NHDFs) (F1MC1, population doubling [PD] = 44.07 at the beginning of the experiment) were treated daily or not with veliparib + H2O2 as in Figure 7. phosphoXRCC1 (A) …
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Figure 7—figure supplement 2—source data 1
Quantification of phosphoXRCC1 foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp2-data1-v1.xlsx
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Figure 7—figure supplement 2—source data 2
Quantification of polynucleotide kinase phosphatase (PNKP) foci.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp2-data2-v1.xlsx
Figure 7—figure supplement 3
Same experiment as in Figure 7 with another normal human dermal fibroblast (NHDF) donor.
NHDFs (F6MC1, population doubling [PD] = 40.04 at the beginning of the experiment) were submitted daily to the combined veliparib +H2O2 treatment as in Figure 6 for 31 days. Then, the H2O2 treatment …
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Figure 7—figure supplement 3—source data 1
Growth curves.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp3-data1-v1.xlsx
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Figure 7—figure supplement 3—source data 2
Quantification of SA-β-Gal assays.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp3-data2-v1.xlsx
Figure 7—figure supplement 4
The combined poly(ADP)ribose polymerase (PARP) inhibitor + H2O2 treatment induces a panel of senescence markers.
Normal human dermal fibroblasts (NHDFs) (F1MC1, population doubling [PD] = 40.01 at the beginning of the experiment) were treated daily or not with veliparib + H2O2 as in Figure 6. (A) At day 25, …
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Figure 7—figure supplement 4—source data 1
Values of C12FDG fluorescence intensity.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp4-data1-v1.xlsx
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Figure 7—figure supplement 4—source data 2
Western blots.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp4-data2-v1.pptx
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Figure 7—figure supplement 4—source data 3
Results of Annexin V/propidium iodide assays.
- https://cdn.elifesciences.org/articles/67190/elife-67190-fig7-figsupp4-data3-v1.xlsx
Author response image 1
Tables
Author response table 1
| Non-irradiated | PTV | Margin (-5 to +20mm) | Margin (+22 to +47mm) | |
|---|---|---|---|---|
| Mean | 2.34 | 7.49 | 2.96 | 3.45 |
| Fold change between PTV and margin | 2.53 | 2.17 |
