巴西学者科学实验颠覆性发现：转基因Bt对老鼠血液有毒性
时间：2013-05-05 09:48:09 来源：作者博客 作者：陈一文
Bt toxins are toxic to the blood of mice
转基因Bt毒素对老鼠血液有毒性
翻译、转载、推荐、评论者：陈一文（cheniwan@cei.gov.cn）
《转基因技术与人类安全》研究专家、80年代前全国青联委员
《新浪网》“陈一文顾问博客”：http://blog.sina.com.cn/cheniwan
转载自《转基因观察》网站：
http://www.gmwatch.org/index.php?option=com_content&view=article&id=14803:bt-toxins-are-toxic-to-the-blood-of-mice
Thursday, 02 May 2013 22:07
2013年5月2日
NOTE:
注：巴西巴西利亚大学生物科学学院遗传学与形态学系研究者们发表在《血液学与血栓栓塞性疾病》的一项新的研究（论文摘要见后边附录），对转基因Bt蛋白在哺乳动物中的毒性进行了探索。他们的研究表明，转基因Bt毒素Cry1Aa, Cry1Ab、Cry1Ac或Cry2A在老鼠血液中产生毒性影响。对老鼠血液的毒性是如何产生的没有清楚的描述，但是有一点描述的非常清楚，即转基因作物监管机构作为批准转基因Bt作物基础的转基因Bt对哺乳动物没有毒性的假定，是伪造的假定。
In insects, Bt toxins exercise their toxic effects by breaking holes in the gut and rupturing the cells. In the mice in this experiment, Bt toxins caused red blood cells to rupture.
在昆虫中，Bt毒素通过肠道中穿孔与破坏细胞发挥其毒性作用。这项实验中的老鼠中，Bt毒素造成红血球细胞破碎。
The study says, "It has been reported that Cry toxins exert their toxicity when activated at alkaline pH of the digestive tract of susceptible larvae, and, because the physiology of the mammalian digestive system does not allow their activation, and no known specific receptors in mammalian intestinal cells have been reported, the toxicity [of] these MCAs [microbial control agents] to mammals would negligible.
该项研究说，“某些研究报告说：Cry毒素在感病幼虫的消化道的碱性pH时发挥它们的毒性，而，因为哺乳动物消化系统的生理学不允许它们活化，而且哺乳动物肠道细胞还没有任何已知的具体受体，因而这些MCA[微生物控制剂]对哺乳动物的毒性作用可以忽略不计。
However, our study demonstrated that Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2A induced hematotoxicity, particularly to the erythroid lineage.
然而，我们的研究演示，被转基因各自表达Cry1Aa、Cry1Ab、Cry1Ac或者Cry2A的Bt孢子晶体诱发恶血液毒性，特别对血液红细胞。
This finding corroborates literature that demonstrated that alkali-solubilized Bt spore-crystals caused in vitro hemolysis in cell lines of rat, mouse, sheep, horse, and human erythrocytes and suggested that the plasma membrane of susceptible cells (erythrocytes, in this case) may be the primary target for these toxins [33]...
这种发现证实了一些科学文献演示的碱性可溶解的Bt孢子晶体在老鼠、小鼠、绵羊、马与人类红血球细胞系中造成试管中溶血作用，并且提议易受感染的细胞（红血球细胞，在这种情况中）可能成为这些毒素的主要目标[33]。
"In conclusion, results showed that the Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2A can cause some hematological risks to vertebrates, increasing their toxic effects with long-term exposure. Taking into account the increased risk of human and animal exposures to significant levels of these toxins, especially through diet, our results suggest that further studies are required to clarify the mechanism involved in the hematotoxicity found in mice, and to establish the toxicological risks to non-target organisms, especially mammals, before concluding that these microbiological control agents are safe for mammals."
“作为结论，结果表明被转基因各自表达Cry1Aa、Cry1Ab、Cry1Ac或者Cry2A的Bt孢子晶体可以对脊椎动物造成某些血液学方面风险，它们的毒性影响长期接触进一步增加。考虑到人类与动物接触相当量这些毒素所增加的风险，特别通过饮食，我们的结果提议，在做出这些微生物学控制剂对哺乳动物是安全的结论前，有必要进行进一步的研究以便搞清小鼠中发现的血液毒性的机制，并且确立对哺乳动物等非靶生物的毒理学风险。”
The toxicity of Bt proteins in mammalian cells was also the subject of an in vitro (test-tube) study (Mesnage et al., 2012). In this study, Bt toxin Cry1Ac was found to be toxic to human cells.
另外一项试管内研究以Bt蛋白在哺乳动物细胞中的毒性为主题（Mesnage et al., 2012）。该项研究发现，Bt毒素Cry1Ac对人类细胞有毒性。
这项研究的摘要：http://onlinelibrary.wiley.com/doi/10.1002/jat.2712/abstract
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Mezzomo, B. P., et al. (2013). Hematotoxicity of Bacillus thuringiensis as spore-crystal strains Cry1Aa, Cry1Ab, Cry1Ac, or Cry2Aa in Swiss albino mice. J Hematol Thromb Dis 1(1).
Mezzomo, B. P., et al.（2013）。作为Cry1Aa、Cry1Ab、Cry1Ac或者Cry2A的孢子晶体的苏云金杆菌（Bt）在瑞士albino小鼠中的血液学毒性。血液学与血栓栓塞性疾病杂志。1(1).
Study available here in full pdf:
论文全文pdf文件：
http://esciencecentral.org/journals/JHTD/JHTD-1-104.pdf
Abstract: Formulated and sporulated cultures of Bacillus thuringiensis (Bt) have been widely used against insect pests, but after the advent of genetically modified plants expressing δ-endotoxins, the bioavailability of Cry proteins has been increased. For biosafety reasons their adverse effects should be studied, mainly for non-target organisms. Thus, we evaluated, in Swiss albino mice, the hematotoxicity and genotoxicity of four Bt spore-crystals genetically modified to express individually Cry1Aa, Cry1Ab, Cry1Ac, or Cry2A, administered alone by gavage with a single dose of 27 mg/ Kg, 136 mg/Kg or 270 mg/Kg, 24 h, 72 h or 7 days before euthanasia. Binary combinations of these four spore-crystal proteins were also assayed at 270 mg/Kg with a single administration 24 h before euthanasia. Control mice received filtered water or cyclophosphamide at 27 mg/kg. For hematotoxicity evaluations, blood samples were drawn by cardiac puncture and processed in a multiple automated hematology analyzer; for genotoxicity analyses, micronucleus test was carried out in mice bone marrow cells. Spore-crystal administrations provoked selective hematotoxicity for the 3 exposure times, particularly for erythroid lineage. A significant reduction in bone marrow cell proliferation demonstrated cytotoxic but not genotoxic effects. These effects persisted for all exposure times, becoming more evident at 7 days. Similar results were observed for binary combinations at 24 h, suggesting that further studies are required to clarify the mechanism involved in the hematotoxicity found in mice, and to establish the toxicological risks to non-target organisms, especially mammals, before concluding that these microbiological control agents are safe for mammals.
摘要：苏云金杆菌（Bt）的配方的与孢子培养液一直广泛用于治理害虫，但是，表达Bt毒素的转基因作物出现以后，Cry蛋白的生物可获得性增加了。为生物安全理由，应当对它们的负面影响，特别对于非靶生物，进行研究。为此，我们在瑞士albino小鼠中，单剂各自表达的四种Cry1Aa、Cry1Ab、Cry1Ac或者Cry2A的转基因Bt孢子晶体的血液毒性与基因毒性进行了评价。服用方式：安乐死前24小时、72小时、7天强饲单剂，比较实验用浓度为27 mg/ Kg、136 mg/Kg或者270 mg/Kg。对这四种孢子晶体的双体也进行了实验，服用方式：安乐死前24小时单剂。对照小鼠喂养过滤水或者环磷酰胺，27 mg/ Kg。为血液毒性评价，用心脏穿刺取血样，在多单元自动血液分析仪中处理；为基因毒性分析，对小鼠骨髓细胞进行了微核试验。服用孢子晶体对三次接触时间激发了有选择性血液毒性，特别对红血球。骨髓细胞增殖显著下降演示了细胞毒素而不是基因毒性影响。这些影响在所有接触时间都出现，七天内最为明显。双体试验在24小时观察到类似的结果，提议，在做出这些微生物学控制剂对哺乳动物是安全的结论前，有必要进行进一步的研究以便搞清小鼠中发现的血液毒性的机制，并且确立对哺乳动物等非靶生物的毒理学风险。
