Page 209 - The Toxicology of Fishes

Biotransformation in Fishes 189

TABLE 4.9
Effects of β-Naphthoflavone (BNF) and 3-Methylcholanthrene (3-MC) on UGT Induction
in Various Fish Species
Maximum
Species Inducer Dose Induction Ref.
Rainbow trout (Oncorhynchus mykiss) BNF 100 mg/kg 3× Andersson et al. (1985)
BNF 50 mg/kg 2× Celander and Forlin (1995)
BNF 5 mg/kg 1.7× LeMaire et al., 1996
Sea bass (Dicentrarchus labrax) 3-MC 20 mg/kg 1.5× LeMaire et al., 1996
BNF 80 mg/kg 1.8× Novi et al. (1998)
BNF 0.3–0.9 µM 3× Gravato and Santos (2002)
aqueous
Dab (Limanda limanda) 3-MC 20 mg/kg No induction LeMaire et al., 1996
Plaice (Pleuronectes platessa) 3-MC 10 mg/kg 1.4× George and Young (1986)
Channel catfish (Ictalurus punctatus) 3-MC 50 mg/kg 1.7× Gaworecki et al. (2004)
Brown bullhead (Ictalurus nebulosus) 3-MC 20 mg/kg 2× Pangrekar and Sikka (1992)
Mummichog (Fundulus heteroclitus) 3-MC 50 mg/kg 1.7–2× Gaworecki (unpublished data)

TABLE 4.10
Effects of PCBs on the Induction of UGTs in Various Fish Species
Dose Maximum
Species Inducer (mg/kg) Induction Ref.

Rainbow trout (Oncorhynchus mykiss) PCB 77, 126 1–5 1.6× Huuskonen et al. (1996)
Clophen A50 100 2× Forlin et al. (1996)
3,3′,4,4′-TCB 0.3 1.75–2× Blom and Forlin (1997)
Brook trout (Salvelinus fontinalis) 3,3′,4,4′-TCB 10 1.5× Boyer et al. (2000)
®
Sand flathead (Platycephalus bassensis) Arochlor 1254 400 1.75× Brumley et al. (1995)

treatment with the potent peroxisome proliferator-activated receptor γ (PPARγ)-mediated peroxisomal
proliferator perfluorooctanoate (PFOA) has not been found to induce UGT1B1 mRNA levels in tissues
other than kidney (Leaver et al., unpublished data). This pattern of induction by BNF and PFOA is
identical to that observed for the glutathione S-transferase gene (GSTA), which contains peroxisomal
proliferator response elements (PPREs) and antioxidant response elements (AREs) but not xenobiotic
response elements (XREs) in the promoter region (Leaver et al., 1997). Exposure to PCBs generally
induces UGT activity in fish species (Table 4.10). When tilapia (Oreochromis niloticus) were fed a diet
amended with sewage sludge, tissue PCB concentrations were increased, together with an increase in
UGT activity (Yang et al., 1993). Coplanar PCBs are AhR ligands; however, when coplanar PCBs are
metabolized by CYP isozymes, the hydroxylated metabolites that are formed can be potent inhibitors
of UGT and sulfotransferase (van den Hurk et al., 2002).

Inhibition of UGTs
Of great environmental concern is inhibition of the steroid-type UGT by environmental pollutants.
Inhibition of these enzymes could cause an accumulation of active hormone that may lead to disturbed
gonadal cycles and even tumor formation in the hormone secreting organs. Some xenoestrogens were
indeed demonstrated to affect UGTs in fish species; for example, nonylphenol inhibited steroid-conju-
gating UGT activity in Atlantic salmon (Arukwe et al., 1997), and nonylphenol diethoxylate inhibited
UGT activity in rainbow trout hepatocytes (Sturm et al., 2001). Growth hormone caused an inhibition
of UGT with testosterone as substrate (Cravedi et al., 1995), indicating that there may be interactions
between different UGT isoforms through their respective substrates. In addition, liver UGTs are important
in the metabolism and excretion of thyroid hormones in fish; thyroid glucuronides have been measured
in the bile of a variety of fish species (George, 1994). In rainbow trout (Oncorhynchus mykiss), injection