beta-Naphthoflavone- and self-induced metabolism of 3,3',4,4'-tetrachlorobiphenyl in hepatic microsomes of the male, pregnant female and foetal rat.
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 beta-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 beta-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 beta-naphthoflavone pretreated male rat, an apparent Km and Vmax of 4.5 microM 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.
Morse
D C
DC
Department of Toxicology, Agricultural University, Wageningen, The Netherlands.
Van Bladeren
P J
PJ
Klasson Wehler
E
E
Brouwer
A
A
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006900:Hydroxylation; D008099:Liver / Q000196:embryology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000378:metabolism* / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D009249:NADP; D019324:beta-Naphthoflavone; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl; D010634:Phenobarbital