Effect of a dioxin-like PCB (CB 126) on the biotransformation and genotoxicity of benzo[a]pyrene in the marine flatfish dab (Limanda limanda)

Two experiments were performed to study the interaction between benzo[a]pyr ene (BaP) and the planar, dioxin-like PCB congener 3,3',4,4',5-pentachlorob iphenyl (CB 126) in the flatfish dab (Limanda limanda). The first experimen t involved four groups. Group I was treated with 10 mu g/kg CB 126, group I I was treated with 2 mg/kg BaP, group III was first treated with 10 mu g/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 mu g/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 signi ficant EROD induction at the 50 mg/kg, but not at the 2 mg/kg level. Concur rent with EROD induction by either CB 126 or 50 mg/kg BaP, was a significan t change in the biliary metabolite pattern in favour of 1-hydroxybenzo[a]py rene and 3-hydroxybenzo[a]pyrene and towards a lower fraction of the procar cinogen BaP-7,8-dihydrodiol (7,8-DIOL). Pre-treatment with CB 126 did not c ause an increase of hepatic BaP DNA adducts formed after treatment with eit her 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 lend to an increase in DNA adduct levels in liver tissue. The observation that the level of 7,S-DIOL is decreased despite a higher (C YP1A mediated) EROD activity explains, at least in part, the lack of induct ion of DNA adducts, (C) 2000 Elsevier Science B.V. All rights reserved.