β-Naphthoflavone- and self-induced metabolism of 3,3′,4,4′-tetrachlorobiphenyl in hepatic microsomes of the male, pregnant female and foetal rat

Abstract

1. The in vitro metabolism of 3,3′,4,4′-tetrachloro-[¹⁴C]-biphenyl ([¹⁴C]-TCB) by hepatic microsomes from the Wistar rat was investigated with liver microsomes from the male, pregnant female and foetus.

2. Three hydroxylated metabolites (4-OH-3,3′,4,5′-tetrachlorobiphenyl, 5-OH-3,3′,4,4′-tetrachlorobiphenyl, and 6-OH-3,3′,4,4′-tetrachlorobiphenyl) were identified by hplc and gc-ms after incubations of liver microsomes from the β-naphthoflavone-pretreated male rat and TCB-treated pregnant rat. No metabolites of [¹⁴C]-TCB were found after incubation with foetal liver microsomes from dams pretreated with [¹⁴C]-TCB. The results indicate that the in vivo accumulation of 4-OH-tetraCB in the foetal compartment is probably due to transplacental transport rather than the formation of this metabolite in the foetus.

3. Pretreatment of the male rat with β-naphthoflavone substantially induced the formation of hydroxylated metabolites, but pretreatment with phenobarbital and dexamethasone was without effect. Based on in vitro incubations of liver microsomes from the β-naphthoflavone pretreated male rat, an apparent K_m and V_max of 4·5 μM and 240 pmol/mg protein/min respectively was determined for the metabolism of [¹⁴C]-TCB. The formation of phenolic metabolites of [¹⁴C]-TCB was most likely dependent on P4501A induction.