Institute of Molecular Biology and Genetics, National Academy of Sciences, Kiev, Ukraine.
Toxicol Lett. 2010 Jul 1;196(2):80-6. doi: 10.1016/j.toxlet.2010.03.1115. Epub 2010 Apr 7.
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.
本研究旨在分析环境氧化应激对来自乌克兰和白俄罗斯放射性污染和化学污染地区足月胎盘人体单加氧酶、谷胱甘肽 S-转移酶（GST）活性和多环芳烃（PAH）-DNA 加合物的影响，并将这些生物标志物与新生儿的整体健康状况进行比较。在接触不同水平放射性和 PAH 污染的妇女群体中测量了胎盘 PAH-DNA 加合物形成、GST 活性、7-乙氧基香豆素 O-去乙基酶（ECOD）活性和硫代巴比妥酸反应物质（TBARS），后者是脂质过氧化的指标。从 143 个人足月胎盘样本中获得的体外代谢数据与母体和新生儿健康指标进行了比较。ECOD 活性最高的是从化学污染地区和放射性污染地区获得的胎盘；与被认为“清洁”的区域相比，ECOD 活性高出 7 倍和 2 倍。健康状况最差的新生儿 GST 活性下降最为明显（144-162mUmgprotein(-1) vs. 258-395mUmgprotein(-1)），ECOD 活性增强，PAH-DNA 加合物形成水平最高。TBARS 水平最高的是接触最高辐射水平的妇女。胎盘解毒效率与产妇年龄和新生儿健康状况呈负相关。环境氧化应激与贫血、威胁性流产、毒血症、胎儿缺氧、自然流产和胎儿生长迟缓有关。我们的数据表明，化学或放射性诱导的氧化应激增强了细胞色素 P450 介导的酶活性，可能导致反应性代谢物的形成增加。GSH 转移酶的活性没有增强。这种解毒能力的失衡可以通过增加 PAH-DNA 加合物的产生、降低脂质过氧化和胎儿健康状况恶化来衡量。
