title: Human placental glutathione S-transferase activity and polycyclic aromatic hydrocarbon DNA adducts as biomarkers for environmental oxidative stress in placentas from pregnant women living in radioactivity- and chemically-polluted regions.
abstract: This study was designed to analyze the effect of environmental oxidative stress on human placental monooxygenases, glutathione S-transferase (GST) activity and polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human term placentas from radioactivity-contaminated and chemically-polluted areas of the Ukraine and Belarus, and to compare these biomarkers to the newborn's general health status. Placental PAH-DNA adduct formation, GST activity, 7-ethoxycoumarin O-deethylase (ECOD) activity, and thiobarbituric reactive substances (TBARS), an index of lipid peroxidation, were measured in groups of women exposed to different levels of radioactivity and PAH pollution. The in vitro metabolism data, obtained from 143 human placental samples at term, were compared to indices of maternal and newborn health. The highest ECOD activity was recorded in placentas obtained from chemically-polluted areas and a radioactivity-contaminated area; the ECOD activity was 7-fold and 2-fold higher compared to the region considered to be "clean". Newborns with the most compromised health status displayed the greatest down-regulation of GST activity (144-162mUmgprotein(-1) vs. 258-395mUmgprotein(-1)), enhanced ECOD activity and the highest level of PAH-DNA adduct formation. The highest level of TBARS was observed in women exposed to the highest levels of radiation. The efficiency of placental detoxification negatively correlated with maternal age and the health status of the newborn. Environmental oxidative stress was related to an increase in anemia, threatened abortions, toxemia, fetal hypoxia, spontaneous abortions and fetal hypotrophy. Our data suggest that chemically- or radioactivity-induced oxidative stress enhance cytochrome P450-mediated enzymatic activities potentially resulting in increased formation of reactive metabolites. The activity of GSH-transferase is not enhanced. This imbalance in detoxification capacity can be measured as increased production of PAH-DNA adducts, decreased lipid peroxidation and compromised fetal health.
authors.affiliation: Institute of Molecular Biology and Genetics, National Academy of Sciences, Kiev, Ukraine.
authors.forename: Maria Yu
authors.initials: MY
authors.lastname: Obolenskaya
authors.forename: Nadiya M
authors.initials: NM
authors.lastname: Teplyuk
authors.forename: Rao L
authors.initials: RL
authors.lastname: Divi
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Poirier
authors.forename: Nataliya B
authors.initials: NB
authors.lastname: Filimonova
authors.forename: Monika
authors.initials: M
authors.lastname: Zadrozna
authors.forename: Markku J
authors.initials: MJ
authors.lastname: Pasanen
mesh_terms: D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D047852:Chernobyl Nuclear Accident; D018736:DNA Adducts / Q000378:metabolism*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000009:adverse effects / Q000378:metabolism*; D005260:Female; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008423:Maternal Age; D018811:Maternal Exposure; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D010641:Phenotype; D010920:Placenta / Q000187:drug effects* / Q000201:enzymology / Q000528:radiation effects*; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology; D002094:Republic of Belarus; D018570:Risk Assessment; D011795:Surveys and Questionnaires; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014455:Ukraine; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018736:DNA Adducts; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D017392:Thiobarbituric Acid Reactive Substances; D015660:7-Alkoxycoumarin O-Dealkylase; D005982:Glutathione Transferase
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