关键词: Cellular model Lymphocyte Lysosome Mitochondria Teratogenic drug

Mesh : Animals Humans Female Pregnancy Flow Cytometry Reactive Oxygen Species Teratogenesis Fetus Teratogens / toxicity Lymphocytes

来  源:   DOI:10.1007/978-1-0716-3625-1_11

Abstract:
Peripheral blood lymphocytes as primary cells can be isolated from human, animal, fetus, and placenta. These cells are an excellent cellular model for the assessment of cytotoxicity, genotoxicity, oxidative stress, and mitochondrial and lysosomal dysfunction induced by drug and chemicals. Moreover, peripheral blood lymphocytes are an easily available source of primary cells appropriate for basic research and in cellular studies regarding teratogenic, genotoxic, and cytotoxic effect of drugs and chemicals. Most drugs and other chemicals that produce birth defects, known as teratogenic agents, produce reactive oxygen species (ROS) formation and mitochondrial and lysosomal dysfunction. It seems that there is an important mechanistic link between oxidative stress, mitochondrial damages, lysosomal integrity, and teratogenic drug-induced birth defects. One of the most sensitive periods in the embryo is transition from an important developmental event to another such as transition from proliferation to differentiation. Mitochondria, lysosomes, and cellular ROS have an important role in proliferative, differentiative, and apoptotic activities during the development. Therefore, disruption of the function of mitochondria, lysosomes, oxidative stress, and redox imbalance leads to cellular dysfunctions and subsequently poor developmental outcomes in the fetus. In this chapter, we will focus on evaluation of mitochondrial/lysosomal functions and estimation of ROS formation using flow cytometry methods in isolated lymphocytes and their isolated mitochondria.
摘要:
外周血淋巴细胞作为原代细胞可以从人类中分离,动物,胎儿,和胎盘。这些细胞是评估细胞毒性的优秀细胞模型,遗传毒性,氧化应激,以及由药物和化学物质引起的线粒体和溶酶体功能障碍。此外,外周血淋巴细胞是一种易于获得的原代细胞来源,适用于基础研究和细胞研究,基因毒性,以及药物和化学物质的细胞毒性作用。大多数产生先天缺陷的药物和其他化学物质,被称为致畸剂,产生活性氧(ROS)形成和线粒体和溶酶体功能障碍。似乎氧化应激之间存在重要的机械联系,线粒体损伤,溶酶体完整性,和致畸药物引起的出生缺陷。胚胎中最敏感的时期之一是从重要的发育事件到另一个发育事件的过渡,例如从增殖到分化的过渡。线粒体,溶酶体,细胞ROS在增殖中具有重要作用,区分性,和发育过程中的凋亡活动。因此,线粒体功能的破坏,溶酶体,氧化应激,和氧化还原失衡导致胎儿的细胞功能障碍和随后的不良发育结果。在这一章中,我们将重点评估线粒体/溶酶体功能,并使用流式细胞术方法评估分离的淋巴细胞及其分离的线粒体中的ROS形成。
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