Article Figures & Data
Figures
- Figure 1.
Effect of chemopreventive agents on liver function in 3-month-old mice. A, liver to body weight (%). White, untreated Mdr2 heterozygotes; black, untreated Mdr2-KO; diagonal hatching, Mdr2-KO treated with tannic acid; gray, Mdr2-KO treated with selenomethionine (four males in each group). B, levels of liver enzymes and cholesterol in serum (units). Abbreviations: TA, tannic acid; SEM, selenomethionine; ALT, alanine aminotransferase; ALP/4, alkaline phosphatase level divided into 4 (to fit to the scale); AST, aspartate aminotransferase; CHOL, cholesterol.
- Figure 2.
Effect of chemopreventive agents on the liver histology and PCNA expression in 3-mo-old mice. Top, H&E staining; middle and bottom, staining with anti-PCNA antibody. +/−, control Mdr2 heterozygous mice. Abbreviations: KO, Mdr2-KO mice; No, no treatment; TA, treatment with tannic acid; SEM, treatment with selenomethionine.
- Figure 3.
Effect of chemopreventive agents on the incidence of liver tumors in 16-mo-old Mdr2-KO mice. A, incidence of tumors with linear size >1 cm. B, incidence of tumors with linear size between 0.5 and 1 cm. No, no treatment (13 males and 8 females); TA, treatment with tannic acid (8 males and 17 females); SEM, treatment with selenomethionine (8 males and 12 females). *, P < 0.05, statistically significant in comparison with untreated animals by Fisher's exact test.
- Figure 4.
Effect of chemopreventive agents on the expression levels of genes differentially expressed in Mdr2-KO mice. A, the reversion indices in a 10-point scale (see Materials and Methods) for untreated Mdr2-KO mutants (Mut) and heterozygotes (Het) and Mdr2-KO mutants treated with tannic acid (MutTA) or selenomethionine (MutSe). The indices are sorted in the order of average treatment effect. B, distance matrix of samples in the space of differentially expressed genes. The matrix was obtained by data reordering using the SPIN algorithm (see Materials and Methods). The distances are color-coded (the warmer the color, the bigger the distance).The sample order is identical in rows and columns (diagonal, distance between each sample and itself). C, distance matrix of samples in the space of significant pairs of genes (see Materials and Methods). The only difference with (B) is the usage of gene expression values relative for pairs of genes instead of individual values.
Tables
- Table 1.
Description of mice sacrificed at different stages of the experiment
No treatment Tannic acid Selenomethionine 3 mo 16 mo 3 mo 16 mo 3 mo 16 mo Mdr2-KO 4 males 13 males 4 males 8 males 3 males 8 males 8 females 17 females 12 females Mdr2+/− 4 males 3 males 3 males 3 males 4 males 8 males 4 females 6 females 6 females - Table 2.
Pathologic scores of liver tissues from 3-mo-old Mdr2-KO and Mdr2+/− control mice either untreated or treated with tannic acid or selenomethionine
Treatment/genotype Ductular proliferation Portal inflammation Fibrosis Mitotic activity Councilman bodies Total score Untreated Mdr2+/− 0 ± 0 0 ± 0 0 ± 0 0.5 ± 0.4 0.3 ± 0.5 0.8 ± 0.5 Mdr2-KO 3.0 ± 0 2.7 ± 0.6 2.3 ± 0.6 0.7 ± 0.5 2.0 ± 1.1 10.7 ± 1.5 Tannic acid treated Mdr2+/− 0 ± 0 0 ± 0 0 ± 0 1.0 ± 1.7 0 ± 0 1.0 ± 1.7 Mdr2-KO 3.0 ± 0 3.0 ± 0 3.0 ± 0 1.0 ± 1.7 0.7 ± 0.6 10.7 ± 2.1 Selenomethionine treated Mdr2+/− 0 ± 0 0 ± 0 0 ± 0 0 ± 0 0.7 ± 0.6 0.7 ± 0.6 Mdr2-KO 2.7 ± 0.6 2.7 ± 0.6 1.3 ± 0.6 0.3 ± 0.6 1.3 ± 0.6 8.3 ± 1.2 NOTE: Pathologic scores were calculated as described in van Nieuwerk et al. (49).
Volume 6, Issue 4
