Figure 3.

TCDD-Elicited Effects on Polyamine (PA) Biosynthesis. (a) Hepatic gene expression associated with PA metabolism was examined using RNA-seq at 28 days repeated TCDD exposure (n = 8). (b) Hepatic PA levels were determined by LC–MS/MS at 28 days repeated TCDD exposure (mean ± s.e.m., n = 5). (c) Hepatic gene expression associated with polyamine metabolism was determined by RNA-seq for a time-course after a bolus dose of 30 µg/kg TCDD. (d) Schematic pathway of hepatic polyamine biosynthesis incorporating fold changes of metabolites (open circle) and gene expression (open rectangle) in male mice orally gavaged with sesame oil vehicle or 30 µg/kg TCDD every 4 days for 28 days. Fold changes of metabolites and gene expression were determined by LC–MS/MS or RNA-seq, respectively. For the heatmaps, the effective dose (ED₅₀), benchmark dose lower limit (BMDL), and relative transcript count (Rel. Count) are denoted. The red/blue color scale represents the log₂(fold change) for differential gene expression. Orange represents the presence of putative dioxin response elements (pDREs). AhR enrichment peaks (FDR ≤ 0.05) are denoted by light green. pDREs found within AHR ChIP-seq enrichment peaks are denoted by garnet. Asterisks (*) denote *p < 0.05 determined by one-way ANOVA with a Dunnett’s post-hoc test. Pound signs (#) denote posterior probabilities P1(t) ≥ 0.80 compared to vehicle.). Official gene name and symbol, and metabolite abbreviations: Amd1 S-adenosylmethionine decarboxylase, Azin1 antizyme inhibitor 1, Oaz1 ornithine decarboxylase antizyme 1, Odc1 ornithine decarboxylase, L-ornithine (ORN), Paox peroxisomal N1-acetyl-spermine/spermidine oxidase, PA polyamine, Sat1 & 2 spermine/spermidine acetyltransferase, Slc3a2 4F2 cell-surface antigen heavy chain, Srm spermidine synthase, Sms spermine synthase, Smox spermine oxidase, SAM S-adenosylmethionine, Decarbox-SAM decarboxylated SAM, MTA methylthioadenosine.