EFFECT OF PRENATAL CHLORDANE ON MACROPHAGE FUNCTION

产前氯丹对巨噬细胞功能的影响

• 批准号: 3250121
• 负责人: John B Barnett
• 金额: $ 11.33万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-06-01 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3250121
• 关键词: RNA biosynthesis; bioassay; chlordane; cytotoxicity; embryo /fetus toxicology; environmental toxicology; enzyme linked immunosorbent assay; genetic strain; histopathology; insecticide biological effect; laboratory mouse; macrophage; messenger RNA; molecular genetics; nuclear runoff assay; prenatal stress

DESCRIPTION: (Adapted from the investigator's abstract) The investigators have shown that prenatal exposure to the polychlorinated hydrocarbon pesticide, chlordane, affects the normal immune ontogeny. They recently found that these prenatally-exposed animals have a severe reduction in the ability of stem cells in the fetal liver, and in 100 and 200 day old bone marrow, to respond to granulocyte/macrophage-colony stimulating factor (GM-CSF) and to recolonize the spleens of irradiated animals (CFU-S) indicating that chlordane may be permanently affecting stem cells during ontogeny. Research is proposed to identify the stage in ontogeny initially affected, i.e., does chlordane have its effect as the pluripotent stem cell prior to its differentiation into a committed progenitor cell, determine the cell cycle stage affected by the chlordane in the target stem cell, and based on this information investigate the mechanistic causes of the defect(s). A goal is to more extensively define the model by determining the timing of the chlordane effects during gestation; determining the fetal-maternal tissue(s) affected by the chlordane; and determining whether the defect can be passed to the progeny (F2) of the affected F1 generation. A functional deficit in macrophages could account for previous reported decreases in DTH, or the consequences of a reduced DTH, as the macrophage plays a large role in the efferent phase of DTH reaction. A plan therefore is to thoroughly examine the macrophage for possible defects by examining the activation pathway of the macrophage at 100 days of age to determine the stage affected, and determine the intracellular location and nature of the defect by examining immunological, biochemical and molecular biological techniques.

描述：（改编自研究者摘要）研究者 已经证明产前接触多氯代烃 杀虫剂氯丹会影响正常的免疫个体发育。 他们最近 发现这些产前暴露的动物的 干细胞在胎肝、100和200天龄骨中的能力 骨髓，对粒细胞/巨噬细胞集落刺激因子有反应 （GM-CSF）和使辐射动物的脾脏集落形成单位（CFU-S） 这表明，氯吡格雷可能会永久性地影响干细胞， 个体发育 研究建议，以确定在个体发育阶段初步 受影响，即，氯霉素作为多能干细胞 在其分化为定向祖细胞之前，确定 靶干细胞中受氯霉素影响的细胞周期阶段，和 根据这些信息，调查 缺陷。 一个目标是更广泛地定义模型， 在怀孕期间的叶绿素效应的时间;确定 受氯霉素影响的胎儿-母体组织;以及 该缺陷可传递给受影响的F1代的后代（F2）。 巨噬细胞的功能缺陷可以解释先前报道的 减少DTH，或减少DTH的后果，如巨噬细胞 在DTH反应的传出相中起重要作用。 因此， 是彻底检查巨噬细胞的可能缺陷， 100日龄时巨噬细胞的活化途径，以确定 受影响的阶段，并确定细胞内的位置和性质， 通过免疫学、生物化学和分子生物学的检查来发现缺陷 技术.