Metabolism of polynuclear aromatic hydrocarbon in human term placenta influenced by cigarette smoke exposure.
The relative contributions of biologic and environmental factors on embryo-fetal development were elucidated in a population of pregnant women who were exposed to varying amounts of active cigarette smoke and women who were not exposed to cigarette smoke. The neonatal weight at birth, placental weight at delivery, duration of pregnancy, and placental xenobiotic (polynuclear aromatic hydrocarbon, PAH) metabolism potential were assessed in this population. The overall metabolic capability in exposed and unexposed placental tissue was measured by in vitro assays using microsomes and a PAH substrate, benzo[a]pyrene (B[a]P). Toxicity potential was determined by B[a]P-metabolite-DNA adduct generation under the same incubation condition. Cigarette smoke exposure increased the overall PAH metabolism potential in placental tissues by approximately 200% (nonsmoker 176.2 +/- 33.6, n = 25; smoker 524.5 +/- 75.5, n = 32 pmol/mg protein) whereas PAH-DNA adduct formation potential did not increase significantly over the basal level (nonsmoker 5002 +/- 830, n = 15; smoker 6172 +/- 1443, n = 22 fmol B[a]P equivalent/mumol DNA/mg protein). Exposure to cigarette smoke during pregnancy is deleterious to fetal development as reflected by reduced neonatal weight at birth. In contrast, placental weight reduction is indistinct, but placentae expressed markedly augmented overall xenobiotic (PAH) metabolism capability in response to cigarette smoke exposure during pregnancy, indicating placental metabolism may be an important mediator of adverse effects induced by such xenobiotic exposure.
Department of Obstetrics and Gynecology, Yale Medical School, New Haven, CT.
M K
MK
Sanyal
Y L
YL
Li
K
K
Belanger
D000704:Analysis of Variance; D001564:Benzo(a)pyrene / Q000378:metabolism / Q000633:toxicity; D001724:Birth Weight; D018736:DNA Adducts / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D009929:Organ Size; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000009:adverse effects / Q000378:metabolism*; D011247:Pregnancy; D012044:Regression Analysis; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism
D018736:DNA Adducts; D011083:Polycyclic Compounds; D001564:Benzo(a)pyrene