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Genes Regulated CYP1A, CYP1B, GST, UGT, NQO CYP1A CYP2B, CYP3A, GST, ABC transporters CYP3A, CYP2B, CYP7A, GST, ABC transporters, AhR CYP4A, CYP7A, CYP8B, LXR CYP7A, ABC transporters, LXR CYP7A, CYP8B, CYP27A, ABC transporters CYP19, Vtg Acyl-coenzyme A dehydrogenase, osteopontin — TAT, CAR, PXR, RXR — — Metallothioneins GST, GCL, NQO

Receptors and Other Ligand-Activated Transcription Factors Potentially Involved in Mechanisms of Toxicity: Diversity in Fish vs. Mammals

Presence and Diversity Fishes Mammals 1–6 (AhR1, 1 (AhR) AhR2, AhR3) 1–2 1 Not found 1 1 1 4–7 3 1 2 2 2 (FXRα, FXRβ) (ERα, ERβa, 3 2 (ERα, ERβ) ERβb) 4–6 3 2 1 2 1 4 3 4 3 1 1 3–5 3 (NRF1, NRF2, NRF3)

Examples of Xenobiotic Ligands or Activators b Dioxins, non-ortho PCBs, some PAHs, etc. None Phenobarbital (PB), TCPOBOP, chlorinated pesticides, ortho-PCBs PB, PCN, ortho-PCBs, organochlorine pesticides, dexamethasone, phthalic acid, nonylphenol Fibrate drugs, phthalate esters GW3965, T0901317 GW4064, 6-α-ethyl- chenodeoxycholic acid Structurally diverse xenoestrogens such as o,p′-DDE, p-nonylphenol Diethylstilbestrol, tamoxifen, bisphen

Examples of Physiological Ligands or Activators a (Bilirubin, biliverdin, tryptophan metabolites, fatty acids) Androstanol/ androstenol (inhibits), lithocholic acid, bilirubin Pregnenalone, corticosterone, bile acids (lithocholic acid) Polyunsaturated fatty acids Cholesterol, 24(S)- hydroxycholesterol Lanosterol, bile acids, chenodeoxycholic acid 17β-Estradiol Unknown 11-Ketotestosterone, dihydrotestosterone Cortisol all-trans-Reti

Dimerization Partner ARNT1 (ARNT2 in vitro) None ARNT RXR RXR RXR RXR RXR ER ERR AR GR RXR Various Zn 2+ — Small Maf proteins NRFs are also known as NFE2-like (NFE2L1, NFE2L2, NFE2L3).

TABLE 5.1 Transcription Factor AhR AhRR CAR PXR (SXR) PPAR LXR FXR ER ERR AR GR RAR RXR MTF NRF c a b c Source: