Fig. 3: Loss of liver p53 leads to hepatic hypertrophy, chronic ROS and DNA damage, and impaired liver function after CCl4-mediated chronic regeneration.

A Quantification of relative hepatocyte size in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice at 7 days after completion of 10-week CCl₄ chronic regeneration regime. N = 9 mice/genotype. Data presented as mean ± SEM and analysed using an unpaired two-tailed t-test with Welch’s correction. **p < 0.01. B H&E and IHC staining for alpha-smooth muscle actin (aSMA), and picrosirius red (PSR) staining in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice at 7 days after completion of 10-week CCl₄ chronic regeneration regime. Scale bars 10 μm. Images representative of N = 10 WT and N = 8 FL mice for H&E, N = 4 WT and N = 5 FL mice for aSMA, and N = 7 mice/group for PSR. C Quantification of IHC staining for aSMA in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice from (B) at either 7 days after completion of 10-week CCl₄ chronic regeneration regime (chronic) or in untreated age-matched mice (control). N = 5 control mice/genotype, N = 4 WT and N = 5 FL chronic mice. Data presented as mean ± SEM and analysed using two-way ANOVA with Holm–Sidak’s multiple comparisons test and multiplicity-adjusted p values. **p < 0.01. D Quantification of staining for picrosirius red (PSR) in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice as in (C). N = 4 control mice/genotype and N = 7 chronic CCl₄ mice/genotype. Data presented as mean ± SEM and analysed using two-way ANOVA with Holm–Sidak’s multiple comparisons test and multiplicity-adjusted p values. **p < 0.01, ***p < 0.001, ****p < 0.0001. Images (E) and quantification (F) of IHC staining MDA, CYP2A5, and gH2AX in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice at 7 days after completion of 10-week CCl₄ chronic regeneration regime as in (C). Scale bars 20 μm. N = 4 mice/group for MDA, N = 7 mice/group for CYP2A5, and N = 9 mice/group for gH2AX. Data presented as mean ± SEM and analysed using two-tailed t-tests and the Sidak–Bonferroni method to account for multiplicity of tests. **p < 0.01, ****p < 0.0001. G Plasma ALT and AST activity (mU/mL) in Albumin-Cre; p53^WT/WT (WT) and Albumin-Cre; p53^FL/FL (FL) mice at 7 days after completion of 10-week CCl₄ chronic regeneration regime. N = 7 mice/group. Each data point represents the mean from technical duplicates per mouse. Data presented as mean ± SEM and analysed using two-tailed t-tests and the Sidak–Bonferroni method to account for multiplicity of tests. ***p < 0.001.