Induction of 7-ethoxyresorufin-O-deethylase (EROD) activity in mice foetuses by the PCB-congener 3,3',4,4'-tetrachlorobiphenyl.
1. 3,3',4,4'-Tetrachlorobiphenyl (TCB) induces liver microsomal 7-ethoxyresorufin-O-deethylase (EROD) activity, and this P450 isoform, i.e. CYP 1, is involved in the metabolism of TCB. 2. TCB administered i.p. to pregnant mice (5-25 mg/kg) induced foetal as well as maternal hepatic EROD activity; in all cases the maternal induced activity was higher than the foetal activity. EROD activity of TCB-induced foetuses increased with developmental age, but decreased with the length of time after treatment. 3. Strain differences were seen; in control mice and TCB-treated dams NMRI > C57BL in EROD activity, but in transplacentally TCB-treated foetuses, C57BL > NMRI. EROD activity in non-pregnant control C57BL mice was higher than in pregnant ones, whereas no activity was seen in control foetuses. 4. Results indicate that TCB at a certain dose can induce foetal metabolism, but that earlier observed foetal accumulation at lower TCB doses is probably a consequence of transplacental transport of maternally-produced metabolites.
Sinjari
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Department of Toxicology, BMC, Uppsala, Sweden.
Törnwall
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Darnerud
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D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010088:Oxidoreductases / Q000096:biosynthesis* / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011247:Pregnancy; D013997:Time Factors
D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1; C028451:3,4,3',4'-tetrachlorobiphenyl