RT Journal Article
SR Electronic
T1 Positional metabolism of benzo(a)pyrene in rat placenta and maternal liver. Comparison of induction effects.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 471
OP 476
VO 14
IS 4
A1 A S Salhab
A1 M O James
A1 S L Wang
A1 K T Shiverick
YR 1986
UL http://dmd.aspetjournals.org/content/14/4/471.abstract
AB The biotransformation of [14C]benzo(a)pyrene (BP) was studied in vitro in the presence of microsomes prepared from isolated labyrinth and basal zone tissues of the rat placenta, as well as from maternal liver. Pregnant rats, day 14 of gestation, received beta-naphthoflavone (beta NF; 15 mg/kg, ip) or 3-methyl-cholanthrene (3MC; 30 mg/kg, ip). On day 15, placentae were dissected and microsomes were incubated with 17 microM [14C]BP and 2 mM NADPH. Metabolites formed in the incubation flasks were extracted and separated by HPLC utilizing a reverse phase column. Only trace BP metabolism occurred in basal zone microsomes from control, beta NF-, or 3MC-pretreated animals, as well as in labyrinth microsomes from control animals. In contrast, the preadministration of beta NF and 3MC increased labyrinth microsomal BP metabolism by 10- to 15-fold. Labyrinth and maternal liver microsomes from beta NF- and 3MC-treated animals actively converted BP to eight separate metabolites which co-chromatographed primarily with quinones and phenols. The overall formation of BP diol and phenolic metabolites by labyrinth microsomes was appreciably less than was observed for liver preparations. The very low activity of BP-4,5-oxide hydrolase in labyrinth microsomes compared to liver may in part explain the low level of formation of BP diols in placental microsomes. Labyrinth microsomes catalyzed the covalent binding of [3H]BP to calf thymus DNA, and this activity increased 5-fold following beta NF pretreatment. A comparison of induced tissues indicates that the amount of DNA binding in labyrinth microsomes is more extensive than would be expected by the level of total BP metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)