Figure 2.

Polyploidy protects from chronic liver injury-induced HCC development. (A) Schema for the DEN + CCl₄ chronic injury experiment. Doxycycline treatment from P0–20 established ploidy differences. At P35, mice were injected with DEN (75 μg/g), followed by biweekly CCl₄ for 12 weeks starting at P38. (B) Representative gross tumor burden from (A). Arrows point to liver surface tumors. (C) Histology shows tumor nodules (circled by dashed yellow lines) from (A). (D) Quantitation of liver to body weight ratios, surface tumors, and tumor nodules from (A) to (C). (E) Schema for the dEn + CCl₄ chronic injury experiment with in vivo siRNA. Scramble (siCtrl) and E2f8 siRNAs in lipid nanoparticles were injected into WT mice starting at P10. A total of 4 injections (2 intraperitoneal and 2 retro-orbital) were performed twice per week. At P35, mice were injected with DEN (75 μg/g), followed by biweekly CCl₄ for 12 weeks starting at P38. (F) Representative gross tumor burden from (E). Arrows point to surface tumors. (G) Histology showing microscopic tumor nodules (circled by dashed yellow lines) from (E). (H) Liver to body weight ratios, surface tumors, and tumor nodules from (E) to (G). (I) Schema for the CCl₄ chronic injury experiment in inducible short hairpin RNA mice. Doxycycline treatment from P0 to P20 established ploidy differences. Starting at P35, mice were injected with biweekly CCl₄ for 20 weeks. (J) All livers from (I) are shown (n = 6 for each group).