Deposition of low dose benzo(a)pyrene into fetal tissue: influence of protein binding.
The influence of maternal binding of benzo(a)pyrene (BaP) on its disposition into fetal tissue was investigated in pregnant Swiss-Webster mice. Low doses (10 ng/mouse) of radiolabeled BaP were administered by intravenous injection on day 15 of gestation. BaP was administered along with normal rabbit serum (NRS) (low binding paradigm) or anti-BaP antiserum (high binding paradigm) and animals killed at various time points. Total radioactivity in the fetus increased with time to peak concentrations in whole fetal homogenates at 12 hours. In contrast, maternal serum, liver, and lung showed a decrease in total radioactivity over the same time period. Total radioactivity/gram of fetal tissue was significantly higher in NRS-treated animals compared to anti-BaP-antiserum-treated animals. Since the levels of the parent compound, BaP, in fetal tissue fell over time similar to maternal liver and lung, the increase in total radioactivity in the fetus was due to an increased concentration of a BaP metabolite fraction in both the low binding and high binding groups. Significantly, a lower level of this metabolite fraction was found in fetal tissue from the anti-BaP-antiserum-treated animals. The present study shows that maternal exposure to this environmental pollutant, even at low doses, results in an accumulation of a metabolite-rich fraction in the fetal compartment, which may contribute to the teratogenic potential of BaP. The data also demonstrate that the amount of this accumulation can be diminished by increasing maternal binding proteins, such as by treatment with anti-BaP antiserum.
McCabe
D P
DP
Department of Pharmacology, UMDNJ-New Jersey Medical School, Newark 07103.
Flynn
E J
EJ
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism* / Q000493:pharmacokinetics; D001769:Blood / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D011247:Pregnancy; D011485:Protein Binding; D014018:Tissue Distribution
D001564:Benzo(a)pyrene