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铅结合蛋白对铅暴露风险评估的意义。

Implications of lead binding proteins for risk assessment of lead exposure.

作者信息

Fowler B A, Kahng M W, Smith D R, Conner E A, Laughlin N K

机构信息

Program in Toxicology, University of Maryland, Baltimore 21201.

出版信息

J Expo Anal Environ Epidemiol. 1993 Oct-Dec;3(4):441-8.

PMID:8173344
Abstract

Lead-binding proteins have previously been isolated from rat and human target tissues. These molecules have shown to possess molecular masses in the general range of 10,000-30,000 daltons. The proteins are acidic in nature and rich in aspartic and glutamic amino acid residues. The molecules in rodents appear to play several important roles in mediating the low dose toxicity of lead in the kidney and brain. Preliminary studies presented in this report indicate that monkeys also possess similar proteins in the kidney and brain, thus providing a biochemical "bridge" in a non-human primate between rodent models and humans. Further, the excretion of these molecules into the urine of rodents increases with lead exposure, suggesting that may also prove useful as biomarkers of lead exposure in humans and monkeys once the dose-range and mechanism(s) of this phenomenon are further defined. Such studies should provide valuable risk assessment information for determining why individuals vary in their susceptibility to lead toxicity.

摘要

此前已从大鼠和人类靶组织中分离出铅结合蛋白。这些分子的分子量一般在10,000至30,000道尔顿之间。这些蛋白质呈酸性,富含天冬氨酸和谷氨酸氨基酸残基。啮齿动物体内的这些分子似乎在介导铅对肾脏和大脑的低剂量毒性方面发挥着几个重要作用。本报告中的初步研究表明,猴子的肾脏和大脑中也存在类似的蛋白质,从而在啮齿动物模型和人类之间的非人类灵长类动物中提供了一个生化“桥梁”。此外,随着铅暴露,这些分子在啮齿动物尿液中的排泄量会增加,这表明一旦进一步确定这种现象的剂量范围和机制,它们也可能被证明是人类和猴子铅暴露的有用生物标志物。此类研究应为确定个体对铅毒性易感性为何存在差异提供有价值的风险评估信息。

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