Table 1.
Organ weights and plasma and hepatic chemistries at the ends of Weeks 52 and 63.
Fig 1.
Gross findings in C57BL/6J mice fed with the control chow diet and CDAA-HF-T(−) at the end of Week 63.
The representative macroscopic appearances of the liver samples at the end of Week 63. CDAA-HF-T(−), choline-deficient, methionine-depleted, L-amino-acid-defined, high-fat diet containing shortening without trans fatty acids.
Fig 2.
Representative histopathology of the mouse liver at the end of Week 63.
Low-power original magnification ×40 (A1, B1, and C1). High-power original magnification ×200 (A2, B2, and C2). Severe lobular inflammation, fibrosis, and numerous foamy macrophages were observed in the liver samples of mice fed with CDAA-HF-T(−) but not of those fed with the control diet. Comparison of Sirius Red-stained areas in control, nontumoral liver area and tumoral liver area of the CDAA-HF-T(−) (D). Results are expressed as percentage of section staining (+) for Sirius Red. *Significantly different from the control group value. #Significantly different from the CDAA-HF-T(−)-Non tumor value.
Fig 3.
Representative histopathology of the proliferative liver lesions at the end of Week 63.
Representative liver for H&E staining that shows RH (A1 and A2), HCA (B1 and B2), and HCC (C1 and C2). Silver impregnation staining confirmed the hepatocyte architectures of RH (A3), HCA (B3), and HCC (C3). The average number of PCNA-positive cells was counted in in control, nontumoral liver area and HCC area of the CDAA-HF-T(−) (D1-4). *Significantly different from the control group value. #Significantly different from the CDAA-HF-T(−)-Non tumor value. Low-power original magnification ×40 (A1, B1, and C1). High-power original magnification ×200 (A/B/C2, A/B/C3 and D). H&E, hematoxylin and eosin staining; HCA, hepatocellular adenoma; HCC, hepatocellular carcinoma; RH, regenerative hyperplasia.
Fig 4.
Representative histopathology of the hemangiosarcoma and cholangiofibrosis at the end of Week 63.
Representative liver for H&E staining that shows HS (A1 and A2) and CF (B1 and B2). Low-power original magnification ×40 (A1 and B1). High-power original magnification ×200 (A2 and B2). CF, cholangiofibrosis; H&E, hematoxylin and eosin staining; HS, hemangiosarcoma.
Table 2.
Microscopic findings in the liver of C57BL/6J mice at the end of Weeks 52 and 63.
Fig 5.
Representative histopathology of the mouse lung at the end of Week 63.
Representative liver for H&E staining that shows control (A) and CDAA-HF-T(−) (B and C). (B) Multiple metastatic nodules. (C) Lymphoid clusters. Original magnification ×40.
Fig 6.
Two-dimensional principal component plot of principal component analysis for RNA-seq.
The X axis indicates the first principal component, whereas the Y axis depicts the second principal component. The value after the principal component identifier refers to the proportion of variance explained by this particular principal component.
Table 3.
Upregulated and downregulated genes in the canonical pathway, CDAA-HF-T(−)-N versus control.
Table 4.
Upregulated and downregulated genes in the canonical pathway, CDAA-HF-T(−)-T versus control.
Table 5.
Upregulated and downregulated genes in the canonical pathway, CDAA-HF-T(−)-T versus CDAA-HF-T(−)-N.
Fig 7.
qPCR and immunohistochemical assessments for MIP-2.
Quantitative real-time PCR data for genes involved in MIP-2 in the liver samples of mice fed with the control chow or CDAA-HF-T(−) for (A) 13 weeks and (B) 63 weeks. *Significantly different from the control group value. Representative immunohistochemical features for MIP-2 in the liver samples of mice fed with the control chow or CDAA-HF-T(−) for (C) 13 weeks and (D) 63 weeks. Original magnification ×200 (C1,2 D1-3), ×100 (D4). Representative liver for immunostaining that shows control chow (C/D1), CDAA-HF-T(−) nontumoral liver tissues (C/D2), CDAA-HF-T(−) hepatocellular carcinoma (D3), and CDAA-HF-T(−) hepatocellular adenoma (D4). Arrows indicate positive staining. CDAA-HF-T(−), choline-deficient, methionine-depleted, L-amino-acid-defined, high-fat diet containing shortening without trans fatty acids.