Molecular Detection-Chromosome Damage-Rodent Germ Cells

分子检测-染色体损伤-啮齿动物生殖细胞

基本信息

批准号：
7161819
负责人：
JACK B BISHOP
金额：
--
依托单位：
NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/7161819
关键词：
biomarker bromine chromosome aberrations cytogenetics developmental genetics early embryonic stage early experience environmental toxicology fluorescent in situ hybridization gene environment interaction germ cells halohydrocarbon laboratory mouse laboratory rat molecular genetics mutagen testing sperm toxicant screening

项目摘要

Infertility and other untoward reproductive and developmental outcomes, such as spontaneous abortion, fetal and neonatal death, birth defects, and genetic susceptibilities to cancer and other diseases, are associated with genetic damage occurring in mammalian germ cells. This Project employs molecular biomarkers in the identification and characterization of chemicals in our environment that are responsible for such germ cell damage. Specifically, fluorescence in situ hybridization (FISH) with chromosome specific DNA markers are used to detect structural and numerical chromosome damage in sperm and early embryonic cells of rodents. These rodent sperm-FISH assays, which provide parallel models of similar sperm-FISH assays in humans, are being used for evaluating the aneugenic and clastogenic potential of environmental chemicals tested in NTP bioassays, as well as for addressing questions about dose response, differential stage sensitivity, the relationship of defects seen in sperm to those transmitted to the early embryo, and other important issues related to health-risks which cannot be addressed in human studies. During this past year, frozen samples of mouse sperm were obtained from RACB studies of Di- and Tri-bromonitromethane and from numerous 90-day Toxicity Studies of NTP compounds. SBIR projects developing automated methods for scoring these sperm samples are near successful completion.

不育以及其他不良生殖和发育结果，例如自发流产，胎儿和新生儿死亡，先天缺陷以及对癌症和其他疾病的遗传敏感性与哺乳动物生殖细胞中发生的遗传损害有关。该项目采用分子生物标志物来鉴定和表征我们环境中造成这种生殖细胞损伤的化学物质。具体而言，使用染色体特异性DNA标记的荧光原位杂交（FISH）用于检测啮齿动物精子和早期胚胎细胞中的结构和数值染色体损伤。这些啮齿动物的精子鱼类测定法提供了类似的人类中类似精子法测定的平行模型，用于评估在NTP生物测定中测试的环境化学物质的动态和碎屑潜力，用于解决剂量反应的问题，以解决这些剂量反应的问题，在差异阶段，与这些相关的缺陷，以及其他相关的缺陷，以及其他相关的缺陷，以及其他相关的问题，以及其他相关的缺陷的关系，以及其他相关的关系。在人类研究中。在过去的一年中，从Di-和三溴硝基甲烷的RACB研究中获得了小鼠精子的冷冻样品，以及从NTP化合物的大量90天毒性研究中获得的。 SBIR项目开发自动化的方法来评分这些精子样本几乎成功完成。