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 (144–162 mU mg protein−1 vs. 258–395 mU mg protein−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.

Transferase activity function and system development process are critical in cattle embryo development

“…Lastly, gene polymerase (DNA directed), gamma 2, accessory subunit ( POLG2, CN440810, OLIGO_08124) is important during the blastocyst stage for mitochondrial DNA transcription and replication (Lloyd et al 2009). These results are consistent with multiple studies that reported under-expression of genes with transferase activity in placental and embryo samples from abnormal relative to normal pregnancies in human and mouse (Prokopenko et al 2002; El-Bassiouni et al 2005; Toledo et al 2006; Rausell et al, 2007; Obolenskaya et al 2010). …”

“…Two examples of this situation are the relative expression level of 1) genes that have transferase activity function between reproductive technologies and 2) genes that are part of system development processes between developmental stages. With respect to the former case, multiple studies have reported difference in the expression of genes that have transferase activity function between normal and abnormal pregnancies at particular stages of mammalian development or tissues sources (Prokopenko et al 2002; El-Bassiouni et al 2005; Toledo et al 2006; Rausell et al, 2007; Obolenskaya et al 2010). However, no study has looked at the differences across stages or tissue sources.…”

Summary of Information on the Effects of Ionizing and Non-ionizing Radiation on Cytochrome P450 and Other Drug Metabolizing Enzymes and Transporters

“…7-Ethoxycoumarin O-deethylation (ECOD) activity was 7-fold and 2-fold higher in human placental microsomes samples (at term) from radioactivity-contaminated areas compared to a region considered to be “clean.” It was suggested that this effect could be related to the increased formation of reactive metabolites in placenta [54]. Experiments performed using animal models (chronic contamination of rats for 9 months by depleted uranium as uranyl nitrate in drinking water, dose of 1 mg/rat/day) showed that the cholesterol-oxidizing enzyme CYP46A1 displayed a 39% increase in mRNA level, as determined by RT-PCR [36].…”

Phenotypic expression and polymorphism of Glutathione S Transferase gene in materno-fetal dyads with idiopathic fetal growth restriction

“…7 It has been revealed that enhanced GST activity in placenta is more beneficial for the health of the newborn. 8 GST exhibits several allelic variants and GSTT1 and GSTM1 are prominent among them. GSTT1/M1 polymorphism has been shown to affect the enzymatic activity and therefore may have some bearing in IFGR.…”