Figure 2 from Small-Molecule Polθ Inhibitors Provide Safe and Effective Tumor Radiosensitization in Preclinical Models
Rodriguez-Berriguete G., Ranzani M., Prevo R., Puliyadi R., Machado N., Bolland HR., Millar V., Ebner D., Boursier M., Cerutti A., Cicconi A., Galbiati A., Grande D., Grinkevich V., Majithiya JB., Piscitello D., Rajendra E., Stockley ML., Boulton SJ., Hammond EM., Heald RA., Smith GCM., Robinson HMR., Higgins GS.
<p>ART558 treatment leads to increased residual IR-induced DNA damage foci. <b>A,</b> γH2AX and 53BP1 foci in HCT116 and H460 cells treated with 3 μmol/L ART558 and 4 Gy IR, assessed at the indicated times points after IR. <b>B,</b> Representative images from irradiated cells from the experiment described in <b>A</b>, at 16 hours after IR. <b>C,</b> Micronuclei in HCT116 and H460 cells treated with 3 μmol/L ART558 and 4 Gy IR, assessed 48 hours after IR. Data points indicate the mean ± SD from triplicate wells and graphs are representative from three separate experiments. <b>D,</b> Representative images from irradiated cells from the experiment described in <b>C</b>. Micronuclei are indicated with arrow heads. dsDNA, double-stranded DNA. <b>E,</b> RAD51 foci in HCT116 and H460 cells treated with 3 μmol/L ART558 and 4 Gy IR, assessed 6 hours after IR. <b>F,</b> Representative images from irradiated cells from the experiment described in <b>E</b>. Lines and error bars in <b>A</b> and <b>E</b> correspond to average ± SD representative from three independent experiments, and statistical significance was calculated using nonparametric one-way ANOVA (Kruskal–Wallis) with Dunn correction for multiple comparisons (*, <i>P</i> < 0.05; **, <i>P</i> < 0.01; ***, <i>P</i> < 0.001; ****, <i>P</i> < 0.0001).</p>