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发表于 2012-1-13 00:15
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加拿大魁北克省几个东部乡镇孕妇与胎儿体内检测出与转基因食品有关联的多种农药成分
Maternal and fetal exposure to pesticides associated to genetically modified foods in Eastern Townships of Quebec, Canada
作者：Aziz Aris (加拿大魁北克省舍布鲁克市中心医院大学妇产科系Department of Obstetrics and Gynecology, University of Sherbrooke Hospital Centre, Sherbrooke, Quebec, Canada，舍布鲁克市中心医院大学临床研究中心Clinical Research Centre of Sherbrooke University Hospital Centre, Sherbrooke, Quebec, Canada, 舍布鲁克市大学医学与健康学院Faculty of Medicine and Health Sciences, University of Sherbrooke, Sherbrooke, Quebec, Canada)Samuel Leblanc (舍布鲁克市大学医学与健康学院)
1. 介绍Introduction
2. 材料与方法 Materials and methods2.1. 化学品与试剂 Chemicals and reagents
2.2. 研究对象与血液样本 Study subjects and blood sampling
2.3. 除草剂与代谢物的测定Herbicide and metabolite determination
2.3.1. 校验曲线Calibration curve
2.3.2. 提取程序 Extraction procedure
2.3.3. 气体色谱法与质谱分析GC–MS analysis
2.4. Cry1Ab杀虫蛋白测定 Cry1Ab protein determination
2.5. 统计分析 Statistical analysis
3. 结果 Results
4. 讨论 Discussion
5. 结论 Conclusions
权益冲突声明 Conflict of interest statement
致谢 Acknowledgements
参考文献 References
摘要
研制出与转基因食品相关联的农药(PAGMF)是为了让转基因作物能够耐受这些农药，例如，草甘磷(GLYP)和草铵磷(GLUF)之类的除草剂或者苏云金杆菌(Bt)细菌毒素之类的杀虫剂。 本次研究旨在评估加拿大魁北克省东部几个乡镇孕妇与胎儿体内所含农药毒素的关联性，并测定所含草甘磷(GLYP)及其代谢物氨甲基磷酸(AMPA)、草铵磷(GLUF)及其代谢物3-甲基磷酸亚基丙酸(3-MPPA)以及Cry1Ab转基因杀虫蛋白(一种Bt毒素) 等毒素的不同含量。我们研究了30位孕妇(PW)和39位非孕妇(NPW)的血液样本。非孕妇血清中检测到了草甘磷(GLYP)和草铵磷(GLUF)，孕妇血清中则未检出。 在孕妇、胎儿和非孕妇血清中检测到了3-甲基磷酸亚基丙酸(3-MPPA)以及Cry1Ab杀虫蛋白毒素。这个研究首次揭示了孕妇和非孕妇体内存在循环的与转基因食品相关联的农药(PAGMF)，为生殖毒理学包括营养与子宫胎盘毒性研究开辟了新的领域。
abstract
Pesticides associated to genetically modified foods (PAGMF) are engineered to tolerate herbicides such as glyphosate (GLYP) and gluphosinate (GLUF) or insecticides such as the bacterial toxin bacillus thuringien-sis (Bt). The aim of this study was to evaluate the correlation between maternal and fetal exposure, and to determine exposure levels of GLYP and its metabolite aminomethyl phosphoric acid (AMPA), GLUF and its metabolite 3-methylphosphinicopropionic acid (3-MPPA) and Cry1Ab protein (a Bt toxin) in Eastern Townships of Quebec, Canada. Blood of thirty pregnant women (PW) and thirty-nine nonpregnant women (NPW) were studied. Serum GLYP and GLUF were detected in NPW and not detected in PW. Serum 3-MPPA and CryAb1 toxin were detected in PW, their fetuses and NPW. This is the first study to reveal the presence of circulating PAGMF in women with and without pregnancy, paving the way for a new field in reproductive toxicology including nutrition and utero-placental toxicities.
4. 讨论
我们的研究结果表明，孕妇和胎儿血液里没有检测到草甘磷(GLYP)，但在一些非孕妇(5%)的血液里有检测到， 然而其代谢物氨甲基磷酸(AMPA)在所有血液样本里均未检测到。这可能是因为没有接触、有效排除或者检测方式的局限。 以前的研究报告指出草甘磷(GLYP)和氨甲基磷酸(AMPA)有着类似的毒理学特征。草甘磷的毒性被证明会引起胎儿骨骼发育迟缓，还会对青春期和成年期的维斯塔（Wistar）雄鼠的生殖系统造成严重不良影响。 而且，草甘磷损害人类胎盘细胞和胚胎干细胞。一个需要注意的有趣现象是，与我们研究中在人体内发现的剂量相比， 在所有的活体动物和试管研究中使用的草甘磷浓度都很高。在这方面，我们的研究结果代表了人体内检测到的实际草甘磷浓度，因此，它们成为该领域未来研究的参考依据。
4. Discussion
Our results show that GLYP was not detected in maternal and fetal blood, but present in the blood of some non-pregnant women (5%), whereas its metabolite AMPA was not detected in all analyzed samples. This may be explained by the absence of exposure, the efficiency of elimination or the limitation of the method of detection. Previous studies report that glyphosate and AMPA share similar toxicological profiles. Glyphosate toxicity has been shown to be involved in the induction of developmental retardation of fetal skeleton and significant adverse effects on the reproductive system of male Wistar rats at puberty and during adulthood. Also, glyphosate was harmful to human placental cells and embryonic cells. It is interesting to note that all of these animal and in vitro studies used very high concentrations of GLYP compared to the human levels found in our studies. In this regard, our results represent actual concentrations detected in humans and therefore they constitute a referential basis for future investigations in this field.
在18%非孕妇血液里检测到了草铵磷，而孕妇和胎儿血液里未检出。相对于草甘磷，没有检测到草铵磷可能是因为没有接触、有效排除或者检测方式的局限。关于与非孕妇相比孕妇体内没有检测到某些化学物质， 大概是怀孕引起的血液稀释造成的， 这至少是一部分原因。另一方面，在100%孕妇和脐带血液样本里以及67%非孕妇血液样本里检测到了3-甲基磷酸亚基丙酸(3-MPPA，草铵磷的代谢物)。这充分说明，这种代谢物比它的前体(即：草铵磷，GLUF)更容易检测到，而且似乎能轻易穿过胎盘进入胎儿体内。加西亚等人研究过人体内草安磷可能的的致畸作用，他们发现，接触草安磷越多，先天性畸形的风险就越大。研究表明，草安磷也造成小鼠胚胎发育迟缓、增加死亡或者发育不全。相对于草甘磷，一个需要注意的有趣现象是，与我们研究中在人体内发现的剂量(53.6ng/ml)相比，在这些动物实验中草安磷的浓度非常高(10ug.ml)。因此，我们的数据提供了这些有毒物质的实际和准确浓度， 这将有助于未来进行更多的相关研究。
GLUF was detected in 18% of non pregnant women’s blood and not detected in maternal and fetal blood. As for GLYP, the non detection of GLUF may be explained by the absence of exposure, the efficiency of elimination or the limitation of the method of detection. Regarding the non-detection of certain chemicals in pregnant women compared with non pregnant women, it is assumed that the hemo dilution caused by pregnancy may explain, at least in part, such non-detection. On the other hand, 3-MPPA (the metabolite of GLUF) was detected in 100% of maternal and umbilical cord blood samples, and in 67% of the non pregnant women’s blood samples. This highlights that this metabolite is more detectable than its precursor and seems to easily cross the placenta to reach the fetus. Garcia et al. investigated the potential teratogenic effects of GLUF in humans and found an increased risk of congenital malformations with exposure to GLUF. GLUF has also been shown in mouse embryos to cause growth retardation, increased death or hypoplasia. As for GLYP, it is interesting to note that the GLUF concentrations used in these tests are very high (10ug/ml) compared to the levels we found in this study (53.6ng/ml). Hence, our data which provide the actual and precise concentrations of these toxicants, will help in the design of more relevant studies in the future.
另一方面， 分别在93%孕妇、80%胎儿和69%非孕妇的血液样本中检测到了Cry1Ab (转基因)杀虫蛋白毒素。尚无其他研究可以与我们的研究结果进行比较。但是，在食用转基因玉米家畜的胃肠道成分里检测到了微量的Cry1Ab抗虫蛋白毒素，进而引起了人们对各种抗虫转基因作物所含的这种毒素的担忧：(1) 这些毒素也许不能有效地排除人体 (2) 食用被(转基因)污染的肉类可能存在(摄入转基因毒素的)高风险。
On the other hand, Cry1Ab toxin was detected in 93% and 80% of maternal and fetal blood samples, respectively and in 69% of tested blood samples from non pregnant women. There are no other studies for comparison with our results. However, trace amounts of the Cry1Ab toxin were detected in the gastrointestinal contents of livestock fed on GM corn, raising concerns about this toxin in insect-resistant GM crops: (1) that these toxins may not be effectively eliminated in humans and (2) there maybe a high risk of exposure through consumption of contaminated meat.
5. 结论
据我们所知，这是首次确证在孕妇、胎儿和非孕妇血液里存在与转基因食品相关联的农药成分的研究。3-甲基磷酸亚基丙酸(3-MPPA)和Cry1Ab杀虫蛋白毒素被明确检测出来，似乎通过胎盘进入胎儿体内。鉴于这些环境污染物可能的毒性以及胎儿的脆弱性，还需要作进一步的研究， 特别是使用胎盘转移法的人士。因此，我们目前的研究结果将为探索有关女性营养学、毒理学和生殖学等未来的新研究领域提供基准数据。现在，与环境化学物质有关的产科-妇科疾病尚不清楚。这可能涉及到围产期并发症(例如流产、早产、子宫内生长受限和先兆子痫)以及生殖疾患(例如不孕症、子宫内膜异位症和妇科癌症)。因此，确定人体内与转基因食品有关联的农药（PAGMF）的浓度就奠定了这个研究领域取得进展的基石。
5. Conclusions
To our knowledge, this is the first study to highlight the presence of pesticides-associated genetically modified foods in maternal, fetal and non pregnant women’s blood. 3-MPPA and Cry1Ab toxin are clearly detectable and appear to cross the placenta to the fetus. Given the potential toxicity of these environmental pollutants and the fragility of the fetus, more studies are needed, particularly those using the placental transfer approach. Thus, our present results will provide baseline data for future studies exploring a new area of research relating to nutrition, toxicology and reproduction in women. Today, obstetric-gynecological disorders that are associated with environmental chemicals are not known. This may involve perinatal complications (i.e. abortion, prematurity, intra uterine growth restriction and preeclampsia) and reproductive disorders (i.e. infertility, endometriosis and gynecological cancer). Thus, knowing the actual PAGMF concentrations in humans constitutes a cornerstone in the advancement of research in this area.
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