Sanders Talia, Liu Yiming, Buchner Virginia, Tchounwou Paul B
Molecular Toxicology Research Laboratory, NIH RCMI - Center for Environmental Health, College of Science, Engineering, and Technology, Jackson State University, Jackson, MS, USA.
Rev Environ Health. 2009 Jan-Mar;24(1):15-45. doi: 10.1515/reveh.2009.24.1.15.
Lead, a systemic toxicant affecting virtually every organ system, primarily affects the central nervous system, particularly the developing brain. Consequently, children are at a greater risk than adults of suffering from the neurotoxic effects of lead. To date, no safe lead-exposure threshold has been identified. The ability of lead to pass through the blood-brain barrier is due in large part to its ability to substitute for calcium ions. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurologic disorders. At the molecular level, lead interferes with the regulatory action of calcium on cell functions and disrupts many intracellular biological activities. Experimental studies have also shown that lead exposure may have genotoxic effects, especially in the brain, bone marrow, liver, and lung cells. Knowledge of the neurotoxicology of lead has advanced in recent decades due to new information on its toxic mechanisms and cellular specificity. This paper presents an overview, updated to January 2009, of the neurotoxic effects of lead with regard to children, adults, and experimental animals at both cellular and molecular levels, and discusses the biomarkers of lead exposure that are useful for risk assessment in the field of environmental health.
铅是一种影响几乎所有器官系统的全身性毒物,主要影响中枢神经系统,尤其是发育中的大脑。因此,儿童比成人更容易遭受铅的神经毒性影响。迄今为止,尚未确定安全的铅暴露阈值。铅能够穿过血脑屏障,这在很大程度上归因于它替代钙离子的能力。在大脑中,铅在前额叶皮质、海马体和小脑中造成的损伤可导致多种神经疾病。在分子水平上,铅干扰钙对细胞功能的调节作用,并破坏许多细胞内的生物活性。实验研究还表明,铅暴露可能具有遗传毒性作用,尤其是在脑细胞、骨髓细胞、肝细胞和肺细胞中。近几十年来,由于有关铅毒性机制和细胞特异性的新信息,铅的神经毒理学知识有了进展。本文概述了截至2009年1月铅在细胞和分子水平上对儿童、成人和实验动物的神经毒性作用,并讨论了在环境卫生领域可用于风险评估的铅暴露生物标志物。