Table 2.
Functional categorization and potential response element regulation of select hepatic genes differentially expressed by 30 μg/kg TCDD, 300 mg/kg PCB153, and MIX.
| Functional category | Gene ID | Gene name | Gene symbol | TCDD* | PCB153* | MIX* | DREsa | PXREsa | CAREsa |
|---|---|---|---|---|---|---|---|---|---|
| 11761 | Aldehyde oxidase 1 | Aox1 | 2.2 | 2.9 | 4.8 | yes | yes | yes | |
| 11997 | Aldo-keto reductase family 1, member B7 | Akr1b7 | NC | 22.1 | 16.8 | yes | yes | yes | |
| 432720 | Aldo-keto reductase family 1, member C19 | Akr1c19 | NC | 1.7 | 2.0 | yes | yes | no | |
| 116852 | Aldo-keto reductase family 1, member C20 | Akr1c20 | −1.7 | −1.6 | −3.0 | no | yes | no | |
| Xenobiotic metabolism/Oxidoreductase activity/Oxidative stress | 13076 | Cytochrome P450, family 1, subfamily a, polypeptide 1 | Cyp1a1 | 348.1 | NC | 348.2 | yes | yes | yes |
| 13077 | Cytochrome P450, family 1, subfamily a, polypeptide 2 | Cyp1a2 | 2.4 | 1.7 | 2.4 | yes | yes | yes | |
| 13088 | Cytochrome P450, family 2, subfamily b, polypeptide 10 | Cyp2b10 | NC | 16.1 | 24.2 | yes | yes | yes | |
| 13089 | Cytochrome P450, family 2, subfamily b, polypeptide 13 | Cyp2b13 | NC | 1.9 | 1.9 | yes | yes | yes | |
| 13094 | Cytochrome P450, family 2, subfamily b, polypeptide 9 | Cyp2b9 | NC | 7.6 | 6.2 | no | yes | yes | |
| 72082 | Cytochrome P450, family 2, subfamily c, polypeptide 55 | Cyp2c55 | NC | 48.4 | 48.4 | yes | yes | yes | |
| 13112 | Cytochrome P450, family 3, subfamily a, polypeptide 11 | Cyp3a11b | −1.9 | 4.0 | 3.1 | yes | yes | yes | |
| 13113 | Cytochrome P450, family 3, subfamily a, polypeptide 13 | Cyp3a13 | −1.9 | 2.5 | NC | no | yes | no | |
| 56388 | Cytochrome P450, family 3, subfamily a, polypeptide 25 | Cyp3a25 | NC | 3.8 | 3.0 | no | yes | yes | |
| 56050 | Cytochrome P450, family 39, subfamily a, polypeptide 1 | Cyp39a1 | NC | 2.5 | 2.0 | yes | yes | no | |
| 14776 | Glutathione peroxidase 2 | Gpx2 | NC | 4.3 | 8.9 | yes | yes | yes | |
| 14858 | Glutathione S-transferase, alpha 2 (Yc2) | Gsta2 | 5.8 | 4.1 | 11.3 | yes | yes | yes | |
| 14863 | Glutathione S-transferase, mu 2 | Gstm2 | 2.0 | 2.0 | 2.2 | yes | yes | yes | |
| 14865 | Glutathione S-transferase, mu 4 | Gstm4 | 2.4 | 4.0 | 5.6 | yes | yes | yes | |
| 14872 | Glutathione S-transferase, theta 2 | Gstt2 | 2.0 | 2.0 | 2.2 | yes | yes | yes | |
| 18104 | NAD(P)H dehydrogenase, quinone 1 | Nqo1s | 4.6 | 2.8 | 12.6 | yes | yes | yes | |
| 76650 | Sulfiredoxin 1 homolog (S. cerevisiae) | Srxn1s | 2.6 | 2.3 | 3.9 | yes | yes | yes | |
| 394435 | UDP glucuronosyltransferase 1 family, polypeptide A6B | Ugt1a6b | 5.6 | NC | 6.4 | yes | yes | no | |
| 22235 | UDP-glucose dehydrogenase | Ugdh | 2.7 | 2.5 | 2.7 | yes | yes | yes | |
| 12491 | CD36 antigen | Cd36 | 5.7 | NC | 6.1 | yes | yes | yes | |
| 26903 | Dysferlin | Dysfs | 3.3 | 1.5 | 14.9 | yes | yes | yes | |
| 170439 | ELOVL family member 6, elongation of long chain fatty acids (yeast) | Elovl6 | −4.3 | −3.8 | −5.2 | yes | yes | yes | |
| Lipid and glucose metabolism | 75497 | Fatty acid binding protein 12 | Fabp12 | 53.7 | −1.5 | 34.4 | yes | yes | yes |
| 14104 | Fatty acid synthase | Fasn | −4.3 | −3.9 | −6.4 | yes | yes | yes | |
| 14718 | Glutamate oxaloacetate transaminase 1, soluble | Got1 | −2.6 | NC | −4.3 | yes | yes | yes | |
| 14571 | Glycerol phosphate dehydrogenase 2, mitochondrial | Gpd2 | −3.0 | 1.5 | −3.3 | yes | yes | yes | |
| 72999 | Insulin induced gene 2 | Insig2 | NC | 5.9 | 4.0 | yes | yes | yes | |
| 53357 | Phospholipase A2, group VI | Pla2g6 | NC | 2.5 | 1.8 | yes | yes | yes | |
| 66350 | Phospholipase A2, group XIIA | Pla2g12as | 3.7 | 2.7 | 7.7 | yes | yes | yes | |
| 228026 | Pyruvate dehydrogenase kinase, isoenzyme 1 | Pdk1 | −1.6 | NC | 1.6 | yes | yes | no | |
| 20250 | Stearoyl-Coenzyme A desaturase 2 | Scd2 | 2.0 | NC | NC | yes | yes | yes | |
| 20788 | Sterol regulatory element binding factor 2 | Srebf2 | −1.7 | −2.1 | −1.6 | yes | yes | yes | |
| 20787 | Sterol regulatory element binding transcription factor 1 | Srebf1 | −2.3 | −2.4 | −4.6 | yes | yes | yes | |
| 12125 | BCL2-like 11 (apoptosis facilitator) | Bcl2l11 | 1.9 | NC | 4.2 | yes | yes | no | |
| Cell cycle/Cell death | 13197 | Growth arrest and DNA-damage-inducible 45 alpha | Gadd45a | −3.6 | 9.4 | 3.1 | yes | no | yes |
| 17873 | Growth arrest and DNA-damage-inducible 45 beta | Gadd45b | 5.7 | 10.8 | 29.2 | yes | yes | yes | |
| 53415 | HIV-1 tat interactive protein 2, homolog (human) | Htatip2 | 3.5 | NC | 4.4 | yes | yes | no | |
| 15937 | Immediate early response 3 | Ier3 | 3.5 | NC | 3.8 | yes | yes | yes | |
| 17869 | Myelocytomatosis oncogene | Myc | 3.0 | 4.2 | 7.2 | yes | yes | yes | |
| 211323 | Neuregulin 1 | Nrg1 | 2.8 | NC | 6.7 | yes | yes | yes | |
| 78688 | Nucleolar protein 3 (apoptosis repressor with CARD domain) | Nol3 | NC | 4.8 | 4.7 | yes | yes | no | |
| 22033 | Tnf receptor-associated factor 5 | Traf5 | 2.1 | NC | 2.3 | yes | yes | yes | |
| 21813 | Transforming growth factor, beta receptor II | Tgfbr2 | 1.6 | 1.8 | 2.4 | yes | yes | yes | |
| 29820 | Tumor necrosis factor receptor superfamily, member 19 | Tnfrsf19 | 3.9 | 2.6 | 7.7 | yes | yes | yes | |
| 21928 | Tumor necrosis factor, alpha-induced protein 2 | Tnfaip2 | 6.7 | NC | 6.9 | yes | yes | yes | |
| 66443 | Tumor necrosis factor, alpha-induced protein 8-like 1 | Tnfaip8l1 | 3.0 | NC | 4.1 | yes | yes | yes | |
| Immune response | 12774 | Chemokine (C-C motif) receptor 5 | Ccr5 | 2.4 | −1.6 | NC | no | yes | yes |
| 56644 | C-type lectin domain family 7, member a | Clec7a | 3.9 | NC | 2.9 | yes | yes | yes | |
| 58239 | Dexamethasone-induced transcript | Dexi | −1.9 | −1.9 | −4.3 | yes | yes | no | |
| 14129 | Fc receptor, IgG, high affinity I | Fcgr1 | 2.4 | NC | 1.9 | yes | yes | no | |
| 14969 | Histocompatibility 2, class II antigen E beta | H2-Eb1 | 7.8 | NC | 5.0 | yes | yes | yes | |
| 14998 | Histocompatibility 2, class II, locus DMa | H2-DMa | 4.0 | NC | 2.7 | yes | yes | yes | |
| 14999 | Histocompatibility 2, class II, locus Mb1 | H2-DMb1 | 4.9 | NC | 3.2 | yes | yes | yes | |
| 15900 | Interferon regulatory factor 8 | Irf8 | 3.1 | NC | 2.0 | yes | yes | yes | |
| 16994 | Lymphotoxin B | Ltb | 2.9 | NC | 2.3 | yes | yes | yes | |
| 17304 | Milk fat globule-EGF factor 8 protein | Mfge8 | 4.6 | NC | 5.0 | yes | yes | yes | |
| 20719 | Serine (or cysteine) peptidase inhibitor, clade B, member 6a | Serpinb6as | 5.1 | NC | 11.0 | yes | yes | yes | |
| 20208 | Serum amyloid A 1 | Saa1 | 3.4 | NC | 3.2 | yes | yes | no | |
| 20209 | Serum amyloid A 2 | Saa2 | 3.2 | NC | 3.2 | yes | yes | yes | |
| 20210 | Serum amyloid A 3 | Saa3 | 7.8 | NC | 3.5 | yes | yes | no |
NC - no change.
Maximum fold change on the microarray (|fold change| >1.5, P1(t) > 0.90).
Putative DNA response elements identified by computational searches (see Materials and Methods).
QRTPCR results. The Agilent microarray Cyp3a11 probe maps the 60-mer region between positions 1105 and 1164 of the Cyp3a11 gene, which is 2053 bp long, while Cyp3a11 primers (listed in a Supplementary Table 3) amplify the 119 bp fragment between 1701 and 1819 bp suggesting that both approaches amplify non-overlapping regions of the gene.
Synergistic response verified by non-linear logistic modeling of QRTPCR dose-response data.