GENETIC TOXICITY IN BACTERIA AND RODENTS

细菌和啮齿动物的遗传毒性

• 批准号: 8429201
• 负责人: LES RECIO
• 金额: $ 154.5万
• 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/8429201
• 关键词: Anabolism; Animal Testing; Animals; Bacteria; Benzene; Benzene Exposure; Biological Assay; Biological Markers; Biological Monitoring; Blood; Blood specimen; Bone Marrow; Brain; Cell Line; Cells; Chemicals; Clinical; Collaborations; Colon; Comet Assay; Contracts; DNA Damage; DNA Repair; Data; Data Collection; Data Set; Dose; Erythrocytes; Event; Exposure to; Family suidae; Frequencies; Future; Genes; Genetic; Goals; Human; In Vitro; Kidney; Laboratories; Liver; Malignant Neoplasms; Micronucleus Tests; Molecular; Mus; Mutagenicity Tests; Mutation; National Institute of Environmental Health Sciences; Outcome; PI-Glycan; Population; Public Health; Radiation; Radio; Rattus; Research Design; Rodent; Role; Sampling; Slide; Speed; Stomach; Support System; System; Testing; Tissues; Toxic effect; base; brain tissue; cancer genetics; cancer risk; cost; genetic profiling; improved; in vivo; innovation; interest; microbial; micronucleus; mutant; peripheral blood; reproductive; research study; tumor; validation studies

The Genetic Toxicity Testing contract provides for the assessment of potential adverse genetic effects from exposure to compounds under study by the NTP. Testing systems employed include both in vitro (animal cell-based and bacterial) and in vivo (rats and mice) assays. Three main tests are conducted routinely: in vitro bacterial mutagenicity assays, in vivo rodent peripheral blood micronucleus (MN) assays, and in vivo rodent DNA damage (Comet) assays in multiple tissues. The MN assays now routinely collect data by flow cytometric analysis of prepared blood samples rather than by scoring slides. This innovation has provided greater ability to detect induced chromosomal damage and has improved the objectivity of the test, as well as the speed of data collection. MN and Comet assays are typically conducted with the same set of animals, thereby maximizing data collection from a single treated animal, reducing animal usage, and reducing costs. During the past fiscal year, 38 microbial mutagenicity assays and 17 in vivo micronucleus assays have been initiated or completed. Sixteen in vivo Comet assays have been conducted in one or multiple tissues including blood, liver, kidney, stomach, colon, and brain. In addition, Comet assays have been conducted in vitro, in collaboration with an NIEHS laboratory, to compare DNA repair activities among several different cell lines in an effort to better understand the role of certain mutant genes associated with particular cancers. An NTP research study designed to examine the effects of low dose benzene exposure in genetically diverse mice has been initiated that may ultimately help to establish lower exposure limits for workers; micronucleus frequencies in blood and bone marrow of benzene-exposed mice will be a major biomarker assessed in this NTP study. During this past fiscal year, another animal mutation endpoint that holds promise for application in human clinical and biomonitoring studies in the future, has been examined in the testing laboratory: the pig-a mutation assay (phosphatidylinositol glycan anchor biosynthesis, class A gene). Mutations in this gene are easily detected in red blood cell samples from laboratory rodents and validation studies in mice have been successfully conducted. During the next fiscal year, we will attempt to multiplex this assay with the in vivo MN and Comet assays, increasing the genetic toxicity information that we obtain from test animals to provide an even more comprehensive profile of the genetic toxicity potential of a chemical.

遗传毒性测试合同规定评估接触国家毒理学方案正在研究的化合物可能产生的不利遗传影响。采用的测试系统包括体外（基于动物细胞和细菌）和体内（大鼠和小鼠）测定。常规进行三项主要试验：体外细菌致突变性试验、体内啮齿动物外周血微核（MN）试验和体内啮齿动物多种组织DNA损伤（彗星）试验。MN检测试剂盒现在通常通过对制备的血液样本进行流式细胞术分析而不是通过对载玻片进行评分来收集数据。这一创新提高了检测诱发染色体损伤的能力，提高了检测的客观性和数据收集的速度。MN和彗星试验通常用同一组动物进行，从而最大限度地从单个治疗动物收集数据，减少动物使用，并降低成本。在上一财年，启动或完成了38项微生物致突变性试验和17项体内微核试验。已在一种或多种组织（包括血液、肝脏、肾脏、胃、结肠和大脑）中进行了16次体内彗星试验。此外，与NIEHS实验室合作，在体外进行了彗星试验，以比较几种不同细胞系之间的DNA修复活性，以更好地了解与特定癌症相关的某些突变基因的作用。一项旨在检查遗传多样性小鼠低剂量苯暴露影响的NTP研究已经启动，这可能最终有助于确定工人的较低暴露限值;苯暴露小鼠血液和骨髓中的微核频率将是本NTP研究中评估的主要生物标志物。在过去的财政年度，另一个动物突变终点有望在未来应用于人类临床和生物监测研究，已在测试实验室进行了检查：猪突变试验（磷脂酰肌醇聚糖锚生物合成，A类基因）。该基因的突变很容易在实验室啮齿动物的红细胞样本中检测到，并且已成功进行了小鼠验证研究。在下一个财政年度，我们将尝试将该试验与体内MN和彗星试验进行复合，增加我们从试验动物中获得的遗传毒性信息，以提供更全面的化学品遗传毒性潜力概况。