Emergence of delayed methylmercury toxicity after perinatal exposure in metallothionein-null and wild-type C57BL mice.
Emergence of delayed methylmercury toxicity after perinatal exposure in metallothionein-null and wild-type C57BL mice.
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DOI：
10.1289/ehp.10906
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发表时间：
2008-06
影响因子：
10.4
通讯作者：
Yasutake, Akira
中科院分区：
文献类型：
--
作者：
Yoshida, Minoru;Shimizu, Natsuki;Suzuki, Megumi;Watanabe, Chiho;Satoh, Masahiko;Mori, Kouki;Yasutake, Akira
尽管已知人类接触甲基汞后会有很长的毒性潜伏期，但很少有动物研究涉及这一问题。证实甲基汞对动物的延迟毒性会影响甲基汞的风险评估。我们在这项研究中的目标是证明存在一个潜伏期的啮齿动物模型中，围产期甲基汞暴露的毒性变得明显，只有在以后的生活。我们的研究包括金属硫蛋白（MT）基因敲除小鼠，因为研究表明，这种菌株的潜在易感性的神经发育毒性的甲基汞。在妊娠期和哺乳早期，MT基因敲除小鼠和野生型C57 Bl/6 J小鼠通过含有5 μg Hg/g的饮食接触甲基汞。在12-13周和52-53周时，我们使用常用的范式检查了后代的行为功能，包括旷场行为（OPF），被动回避（PA）和Morris水迷宫（MM）。在12周龄时，没有检测到甲基汞的行为影响，除了在甲基汞暴露MT-null女性的OPF性能。在52周龄时，甲基汞暴露组在PA和MM中表现较差，其OPF活性与对照组不同。甲基汞的这些影响在无MT菌株中似乎被夸大了。大脑汞浓度在13周龄时趋于稳定。结果表明，围产期暴露于低水平的甲基汞后存在一个长的潜伏期，其中的行为效应出现后，脑汞水平的平稳了很长一段时间。因此，造成晚期效应的最初毒理学事件应该发生在脑汞水平稳定之前。
Although a long latency period of toxicity after exposure to methylmercury (MeHg) is known to exist in humans, few animal studies have addressed this issue. Substantiation of delayed MeHg toxicity in animals would affect the risk evaluation of MeHg. Our goal in this study was to demonstrate the existence of a latency period in a rodent model in which the toxicity of perinatal MeHg exposure becomes apparent only later in life. Our study included metallothionein (MT) knockout mice because studies have suggested the potential susceptibility of this strain to the neurodevelopmental toxicity of MeHg. Pregnant MT-null and wild-type C57Bl/6J mice were exposed to MeHg through their diet containing 5 μg Hg/g during gestation and early lactation. We examined behavioral functions of the offspring using frequently used paradigms, including open field behavior (OPF), passive avoidance (PA), and the Morris water maze (MM), at ages of 12–13 and 52–53 weeks. At 12 weeks of age, behavioral effects of MeHg were not detected, except for OPF performance in MeHg-exposed MT-null females. At 52 weeks of age, the MeHg-exposed groups showed poorer performance both in PA and MM, and their OPF activity differed from controls. These effects of MeHg appeared exaggerated in the MT-null strain. The brain Hg concentration had leveled off by 13 weeks of age. The results suggest the existence of a long latency period after perinatal exposure to low-level MeHg, in which the behavioral effects emerged long after the leveling-off of brain Hg levels. Hence, the initial toxicologic event responsible for the late effects should have occurred before this leveling-off of brain Hg.
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影响因子：
2.9
作者：
Acevedo, SF;Ohtsu, H;Raber, J
通讯作者：
Raber, J
影响因子：
4.8
作者：
Ausó, E;Lavado-Autric, R;Berbel, P
通讯作者：
Berbel, P
影响因子：
2.7
作者：
GOWER, AJ;LAMBERTY, Y
通讯作者：
LAMBERTY, Y
DOI：
10.1093/jnen/62.8.835
发表时间：
2003-08-01
影响因子：
3.2
作者：
Kakita, A;Inenaga, C;Takahashi, H
通讯作者：
Takahashi, H
DOI：
10.1073/pnas.90.17.8088
发表时间：
1993-09-01
影响因子：
11.1
作者：
MICHALSKA, AE;CHOO, KHA
通讯作者：
CHOO, KHA