Effect of a dioxin-like PCB (CB 126) on the biotransformation and genotoxicity of benzo
Two experiments were performed to study the interaction between benzo[a]pyrene (BaP) and the planar, dioxin-like PCB congener 3,3',4,4',5-pentachlorobiphenyl (CB 126) in the flatfish dab (Limanda limanda). The first experiment involved four groups. Group I was treated with 10 µg/kg CB 126, group II was treated with 2 mg/kg BaP, group III was first treated with 10 µg/kg CB 126 and exposed to 2 mg/kg BaP 6 days later, and group IV was a control group. The second experiment was similar, except that the BaP dosage level was increased to 50 mg/kg. Pre-treatment with 10 µg/kg of CB 126 always caused the induction of hepatic cytochrome P450 1A (CYP1A), as measured by significant increases of the model reaction 7-ethoxyresorufin-O-deethylase (EROD) in microsomal preparations. Treatment of dab with BaP caused a significant EROD induction at the 50 mg/kg, but not at the 2 mg/kg level. Concurrent with EROD induction by either CB 126 or 50 mg/kg BaP, was a significant change in the biliary metabolite pattern in favour of 1-hydroxybenzo[a]pyrene and 3-hydroxybenzo[a]pyrene and towards a lower fraction of the procarcinogen BaP-7,8-dihydrodiol (7,8-DIOL). Pre-treatment with CB 126 did not cause an increase of hepatic BaP DNA adducts formed after treatment with either 2 or 50 mg/kg BaP. Glutathione S-transferase (GST) activities remained also unaffected by any of the treatments. The results of this study suggest that the pattern of BaP metabolites in bile depends on the level of CYP1A induction. Moreover, the concurrence of a potent CYP1A inducer and BaP does not necessarily lead to an increase in DNA adduct levels in liver tissue. The observation that the level of 7,8-DIOL is decreased despite a higher (CYP1A mediated) EROD activity explains, at least in part, the lack of induction of DNA adducts.
van Schanke A
Department of Marine Biogeochemistry and Toxicology, Netherlands Institute for Sea Research (NIOZ), PO Box 59, 1790 AB, Den Burg Texel, The Netherlands
Boon
JP
Aardoom
Y
van Leest A
van Schooten FJ
Maas
L
van den Berg M
Everaarts
JM