Maternal Smoking Increases Xenobiotic Metabolism in Placenta but Not Umbilical Vein Endothelium

Abstract

umbilical vein endothelium from these same pregnancies was unaffected by maternal smoking and remained low. In order to confirm that AHH present in endothelium was inducible, we also demonstrated dose-dependent increases in AHH activity in primary cultures of human umbilical vein endothelial cells exposed to PAHs. These findings may indicate first pass protection of the fetus by placental xenobiotic metabolism, or that endogenous factors suppress AHH induction in the fetus but not placenta. may contribute to the development of certain birth defects (4,16,17). Although complex mixtures of chemicals contained in cigarette smoke have been described, little is known about the mechanisms by which these compounds may be embryopathic or about how the human conceptus can be protected from such chemical toxicity.In order to approach these problems, we have been studying the effects of maternal smoking on xenobiotic metabolism in human placenta, concentrating on AHH, a cytochrome P-450 monooxygenase system which increases its activity when mothers smoke (14,20,24,29,30). AHH catalyzes the first step in the metabolism of several of the toxins absorbed from cigarette smoke including PAHs. These compounds, which are concentrated in cigarette smoke, have been found to be carcinogenic, mutagenic, and teratogenic in animals (5). The consequences of increased placental AHH activity in response to maternal smoking are unknown. On the one hand, microsomes from placentas from smokers have been shown to metabolize certain PAHs to mutagenic products in vitro (15). On the other hand, AHH participates in the clearance of toxins such as PAHs in vivo (18,23), and increased placental activity may reduce levels of toxic PAHs in fetal tissues. Hence, increased placental AHH, coupled with a toxic load of PAHs from maternal smoking, could theoretically protect or endanger the developing fetus.Because we are unable to measure placental clearance of PAHs directly in humans, we decided to approach the question of the role of placental PAH metabolism indirectly by comparing effects of cigarette smoking on placenta and a fetal tissue immediately distal to it, umbilical vein endothelium. We hypothesized that if increased placental AHH activity were involved in effectively decreasing levels of PAHs in distal tissues, then we would expect distal tissues to be less affected than the placenta by maternal cigarette smoke. We used AHH activity itself as a measure of PAH exposures and measured activity in placentas and umbilical vein endothelium from smoking and nonsmoking women. We report that while AHH activity in placenta is markedly increased by maternal cigarette smoking, activity in umbilical vein endothelium is not. MATERIALS AND METHODSProcurement of tissues. Placentas were collected at the time of delivery. Several representative samples of villous tissue were immediately removed and frozen at -70" C. Umbilical cords were removed and refrigerated no longer than 8 h prior to use. Cords were used only if they contained untraumatized segments greate...

Relationship between ambient air pollution and DNA damage in Polish mothers and newborns.

“…There are several explanations for the fact that the relationship between ambient air pollution and adduct levels was similar for maternal and newborn WBCs, whereas the relationship between cigarette smoke exposures and adduct levels differed for mother and newborns. Cigarette smoke may induce more Phase I metabolism in the maternal than in the fetal tissues, or induction of CYPIAJ in placentas of smokers may modulate the biologically effective dose to the fetus (47,48). Consistent with our findings, previous studies of adult populations have seen significant associations between active smoking and WBC PAH-DNA adduct levels (16,49,50), although results have not been consistent (51).…”

The Impact of Polycyclic Aromatic Hydrocarbons and Fine Particles on Pregnancy Outcome

“…The ability of PAHs to reach placental tissue has been suggested in many experimental and human studies of aryl hydrocarbon hydroxylase (AHH) activities in placenta and cord blood (26)(27)(28)(29). Hatch at al.…”

Molecular epidemiologic research on the effects of environmental pollutants on the fetus.

“…Supporting the use of peripheral blood cells as a surrogate for target tissue, experimental and human studies indicate comparable levels of DNA adducts across many tissues, including peripheral blood (88,95 (112,113). Evidence suggests that CYPlAI activity in the placenta reduces transfer of PAH to the fetus (114,115 Levels of respirable particulates are also high in Krakow. During 1991, the year prior to the birth of the infants in our study, annual average levels of respirable particulates (< 10 mm in diameter) were 78 pg/m3 in the high pollution area and 38 pg/m3 in the low-pollution area of the city.…”