GENETIC TOXICITY IN BACTERIA AND RODENTS

细菌和啮齿动物的遗传毒性

• 批准号: 7922238
• 负责人: LES RECIO
• 金额: $ 300万
• 依托单位: INTEGRATED LABORATORY SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2013-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7922238
• 关键词: GENETIC; TOXICITY; BACTERIA; RODENTS

25 microbial mutagenicity assays have been completed and 22 in vivo micronucleus assays have been finalized during the fiscal year. At ILS, a comparative study of micronucleus (MN) enumeration in mice and rats by flow cytometry (FCM) and microscopy for 4 chemicals has been completed and the data published. Technology transfer and proficiency at ILS using a flow-based MN determination method has been demonstrated and based on the results of the comparative study mentioned above, the automated flow-based procedure has now replaced the more labor-intensive and less robust slide-based method. The NTP Genetic Toxicity data base has been updated to accept the new flow-derived data, and the data analysis methods have been updated and programmed into the data base, providing more appropriate methods of analyzing the larger number of cells scored with the automated flow cytometry system. Quantification of the fluorescence intensity for each MN as a potential marker for aneuploidy appears to be useful and is routinely done in those studies that show an elevated frequency of MN following exposure to a chemical. The Comet assay for measuring DNA damage levels is being used at ILS in these same in vivo studies; a variety of tissues are being analyzed for induced DNA damage in both the acute and the subchronic dosing studies. NTP is building a data base from which to determine if routinely combining Comet analysis with MN analysis in NTP study animals provides added benefit to assessing chemical toxicity. Sperm samples from mice exposed to a known inducer of chromosomal damage in somatic cells are being analyzed using the sperm FISH CT8 assay to determine if increased levels of chromosomal damage are detected in germ cells as a consequence of exposure to this compound. This exercise is being conducted to help better define the sensitivity of the CT8 assay in detecting germ cell mutagens. Keywords: Micronuclei; Ames test; salmonella; mutation; chromosomal damage

在本财政年度内，已完成25项微生物致突变性试验，并完成了22项体内微核试验。 在ILS，通过流式细胞术（FCM）和显微镜对4种化学品进行小鼠和大鼠微核（MN）计数的比较研究已经完成，并发表了数据。ILS使用基于流动的MN测定方法的技术转移和熟练程度已得到证明，并且基于上述比较研究的结果，基于流动的自动化程序现已取代劳动密集型和稳健性较低的基于载玻片的方法。更新了NTP遗传毒性数据库，以接受新的流式细胞衍生数据，并更新了数据分析方法，并将其编程到数据库中，提供了更适当的方法来分析使用自动流式细胞术系统评分的大量细胞。 作为非整倍性的潜在标志物，每个MN的荧光强度的定量似乎是有用的，并且在那些显示暴露于化学品后MN频率升高的研究中常规进行。 ILS在这些相同的体内研究中使用了用于测量DNA损伤水平的彗星试验;在急性和亚慢性给药研究中，正在分析各种组织诱导的DNA损伤。 NTP正在建立一个数据库，以确定NTP研究动物中常规结合彗星分析和MN分析是否为评估化学毒性提供了额外的益处。使用精子FISH CT 8试验分析暴露于已知的体细胞染色体损伤诱导剂的小鼠精子样本，以确定是否由于暴露于该化合物而在生殖细胞中检测到染色体损伤水平增加。 进行这项工作是为了帮助更好地确定CT 8检测试剂盒在检测生殖细胞诱变剂方面的灵敏度。 关键词：微核;艾姆斯试验;沙门氏菌;突变;染色体损伤