Metabolism of polynuclear aromatic hydrocarbon in human term placenta influenced by cigarette smoke exposure

Sanyal, Mrinal K.; Li, You-Lan; Belanger, Kathleen

doi:10.1016/0890-6238(94)90081-7

Cited by 24 publications

(16 citation statements)

References 31 publications

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“…Several prior studies using the 32P-postlabeling method, which measures a broad spectrum of adducts bound to DNA, have seen an association between maternal smoking and adduct levels in fetal samples (52)(53)(54). However, studies using methodologies specific to PAH-DNA adducts have not (52,55,56).…”

Section: Discussionmentioning

confidence: 99%

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

Whyatt

Santella

Jędrychowski

et al. 1998

Environ Health Perspect

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Industrialized regions in Poland are characterized by high ambient pollution, including polycyclic aromatic hydrocarbons (PAHs) from coal burning for industry and home heating. In experimental bioassays, certain PAHs are transplacental carcinogens and developmental toxicants. Biologic markers can facilitate evaluation of effects of environmental PAHs on the developing infant. We measured the amount of PAHs bound to DNA (PAH-DNA adducts) in maternal and umbilical white blood cells. The cohort consisted of 70 mothers and newborns from Krakow, Poland, an industrialized city with elevated air pollution. Modulation of adduct levels by genotypes previously linked to risk of lung cancer, specifically glutathione S-transferase Ml (GSTM1) and cytochrome P4501A1 (CYP1A1) Mspl restriction fragment length polymorphism (RFLP), was also investigated. There was a dose-related increase in maternal and newborn adduct levels with ambient pollution at the women's place of residence among subjects who were not employed away from home (p<0.05). Maternal smoking (active and passive) significantly increased maternal (p<0.01) but not newborn adduct levels. Neither CYP1A1 Mspl nor GSTM1 polymorphisms was associated with maternal adducts. However, adducts were significantly higher in newborns heterozygous or homozygous for the CYP1A1 Mspl RFLP compared to newborns without the RFLP (p=0.04).Results indicate that PAH-induced DNA damage in mothers and newborns is increased by ambient air pollution. In the fetus, this damage appears to be enhanced by the CYP1A1 Mspl polymorphism.Environ Health Perspect 106(Suppl 3):821-826 (1998). http.//ehpnetl.niehs.nih.gov/docs/1998/ Suppl-3/821-826whyattlabstract html

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Section: Discussionmentioning

confidence: 99%

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

Whyatt

Santella

Jędrychowski

et al. 1998

Environ Health Perspect

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“…In experimental studies, there is a high correlation between DNA adduct formation and carcinogenicity for a series of mutagens/carcinogens, including B[a]P (89,90,94). 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.…”

Section: Moleculamr Epdemiology and Biomakrmentioning

confidence: 99%

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

Perera

Jedrychowski

Rauh

et al. 1999

Environ Health Perspect

277

183

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Evidence shows that fetuses and infants are more affected than adults by a variety of environmental toxicants because of differential exposure, physiologic immaturity, and a longer lifetime over which disease initiated in early life can develop. In this article we review data on the effects of in utero exposure to common environmental contaminants, including polycyclic aromatic hydrocarbons (PAH), particulate matter and environmental tobacco smoke (ETS). We then summarize results from our molecular epidemiologic study to assess risks from in utero exposures to ambient air pollution and ETS. This research study, conducted in Poland, used biomarkers to measure the internal and bioeffective dose of toxicants and individual susceptibility factors. The study included 160 mothers and 160 newborns. Ambient air pollution was significantly associated (p < 0.05) with the amount of PAH bound to DNA (PAH-DNA adducts) in both maternal and infant cord white blood cells (WBC). Newborns with elevated PAH-DNA adducts (greater than the median) had significantly decreased birth weight (p = 0.05), birth length (p = 0.02), and head circumference (p = 0.0005) compared to the newborns with lower adducts (n = 135). Maternal and infant cotinine levels were increased by active and passive cigarette smoke exposure of the mother (p < 0.01). An inverse correlation was seen between newborn plasma cotinine (nanograms per milliliter) and birth weight (p = 0.0001) and length (p = 0.003). Adducts were elevated in placental tissue and WBC of newborns who were heterozygous or homozygous for the cytochrome P4501A1 MspI restriction fragment length polymorphism (RFLP) compared to newborns without the RFLP. Levels of PAH-DNA and cotinine were higher in newborns than mothers. These results document that there is significant transplacental transfer of PAH and ETS constituents from mother to fetus; that PAH-DNA adduct levels in maternal and newborn WBC were increased with environmental exposure to PAH from ambient pollution; and that the fetus is more sensitive to genetic damage than the mother. The study also provided the first molecular evidence that transplacental PAH exposure to the fetus is compromising fetal development. If confirmed, these findings could have significant public health implications since a number of studies have found that reduction of head circumference at birth correlates with lower intelligence quotient as well as poorer cognitive functioning and school performance in childhood. Key words: air pollution, cigarette smoking, CYP1A1 MspI RFLP, GSTM1, newborns, PAH-DNA adducts, Poland. -Environ Health Perspect 107(suppl 3): 451-460 (1999). http://ehpnet 1. niehs. nih.gov/docs/1 999/suppl-3/451-460perera/abstract html The context of the work reviewed here is the growing awareness of the vulnerability of the developing fetus and child to certain environmental contaminants, including those commonly found in urban areas around the world. Following a summary of the toxicity and occurrence of polycyclic aromatic hydrocarbons (PAH), partic...

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“…Our previous study showed that the influence of active maternal cigarette smoke exposure on the in vitro metabolism of a PAH substrate (B[a]P) by placental microsomal cell fractions was variable (Sanyal et al, 1994). The present study is an extension of this study exploring the features of variability related to overall metabolism and reactive product generation from B[a]P substrate induced by such exposure.…”

Section: Introductionmentioning

confidence: 89%

“…They may accumulate in the human placenta, cross the placental barrier during pregnancy, and produce genotoxicity to the developing conceptus (Autrup and Vestergaard, 1996;Gladden et al, 2000;Miller, 2004). However, effects of maternal cigarette smoke on fetal and placental development assessed by weights of the neonate and placenta at delivery, and the overall placental metabolism of exposure substrates were variable ranging from significantly reduced to apparently normal (Sanyal et al, 1994).…”

Section: Introductionmentioning

confidence: 94%

“…Placental microsomes from smoker-or nonsmokerdonors were incubated for 60 min with radiolabeled B[a]P (80 nM B[a]P mixed with [1,3,6-3 H]-B[a]P; Specific Activity 60 Ci/mmol; New England Nuclear, Boston, MA) per mg microsomal protein and a NADP/NADPH generating system described previously (Sanyal et al, 1994). Reactive metabolites produced from B[a]P were quantified by incubating the same placental microsomes separately with radiolabeled B[a]P and salmon sperm DNA.…”

Section: B[a]p Hydroxylase Activity and B[a]p-metabolite-dna Adduct Amentioning

confidence: 99%

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Differential metabolism of benzo[α]pyrene in vitro by human placental tissues exposed to active maternal cigarette smoke

Sanyal

2007

Birth Defects Research Pt B

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Metabolism of polynuclear aromatic hydrocarbon in human term placenta influenced by cigarette smoke exposure

Cited by 24 publications

References 31 publications

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

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

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

Differential metabolism of benzo[α]pyrene in vitro by human placental tissues exposed to active maternal cigarette smoke

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