Lipid peroxidation-coupled co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-dihydrodiol in human term placental microsomes.
The link between lipid peroxidation and benzo(a)pyrene activation was studied in microsomes isolated from human term placenta. Lipid peroxidation was initiated in the presence of NADPH by partially chelated iron. Covalently bound and free metabolites of benzo(a)pyrene or benzo(a)pyrene-7,8-diol were quantitated by radiometry and/or HPLC. Peroxidative conditions increased the amounts of benzo(a)pyrene-trans-anti-tetrol produced from benzo(a)pyrene-7,8-diol, benzo(a)pyrene-diones from benzo(a)pyrene, and protein bound metabolites from both. A reactive oxo-iron complex is proposed as an ultimate species initiating hydrogen abstraction and lipid peroxidation. It is suggested that partially chelated iron catalyzes co-oxygenation of benzo(a)pyrene and benzo(a)pyrene-7,8-diol by peroxyl radical in placental microsomes. This peroxidative reaction may be crucial for bioactivation of benzo(a)pyrene in human term placenta.
Byczkowski
J Z
JZ
Florida Toxicology Research Centre, College of Public Health, University of South Florida, Tampa 33612-3899.
Kulkarni
A P
AP
D001564:Benzo(a)pyrene / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007501:Iron / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology*; D008861:Microsomes / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy
D004101:Dihydroxydihydrobenzopyrenes; C017228:benzo(a)pyrene 7,8-dihydrodiol; D001564:Benzo(a)pyrene; D007501:Iron