Genetic Toxicity Testing Services for the NTP

NTP 基因毒性测试服务

• 批准号: 8948726
• 负责人: LES RECIO
• 金额: $ 87.87万
• 依托单位: INTEGRATED LABORATORY SYSTEMS, LLC
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-19 至 2014-08-03
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8948726
• 关键词: Anabolism; Animal Testing; Animals; Biological; Biological Assay; Biological Monitoring; Blood; Blood specimen; Brain; Cells; Chemicals; Clinical; Clinical Research; Colon; Comet Assay; Contracts; Coupled; DNA Damage; Data; Data Collection; Data Set; Enrollment; Erythrocytes; Event; Exposure to; Family suidae; Future; Gene Mutation; Genes; Genetic; Goals; Health; Human; In Vitro; International; Kidney; Laboratories; Leadership; Liver; Measures; Methods; Micronucleus Tests; Molecular; Mus; Mutagenicity Tests; Mutation; National Institute of Environmental Health Sciences; Outcome; PI-Glycan; Pharmaceutical Preparations; Population; Protocols documentation; Rattus; Rodent; Rodent Model; Sampling; Services; Slide; Speed; Stomach; Support System; System; Testing; Tissues; Toxic effect; Toxicity Tests; Toxicogenetics; Translating; Update; Work; base; cancer genetics; cancer risk; cost; environmental agent; genetic profiling; genotoxicity; human subject; improved; in vivo; innovation; microbial; micronucleus; peripheral blood; pollutant

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 approach 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, approximately 11 microbial mutagenicity assays and 9 in vivo micronucleus assays have been initiated or completed. 40 in vivo Comet assays have been conducted in one or multiple tissues including blood, liver, kidney, stomach, colon, and brain. During the next fiscal year, additional emphasis is expected on in vitro measures of gene mutation and chromosomal damage so as to continue to reduce and refine our use of whole animal tests. 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 investigated 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 updated methods to streamline the assay have been developed, so that integration into existing toxicity tests can be more be accomplished. 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. Currently, 2 pig-a studies are planned, coupled with MN studies integrated into existing NTP toxicity studies. In addition to the animal work conducted for NTP, we have begun a study in human subjects enrolled at the NIEHS Clinical Research Unit aiming to translate our findings in animals to potential biological effects in humans who regularly use an herbal product that NTP is extensively analyzing in rodent models.

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。这一方法提高了检测诱发染色体损伤的能力，并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，已启动或完成了约11项微生物致突变性试验和9项体内微核试验。已经在一种或多种组织中进行了40次体内彗星试验，包括血液、肝脏、肾脏、胃、结肠和大脑。在下一个财政年度，预计将进一步强调基因突变和染色体损伤的体外测量，以继续减少和改进我们对整个动物试验的使用。在过去的财政年度中，在检测实验室中研究了另一种有望在未来应用于人类临床和生物监测研究的动物突变终点：猪-a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，并且已经开发了简化检测的更新方法，以便更好地整合到现有的毒性测试中。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。目前，计划进行2项pig-a研究，并将MN研究纳入现有NTP毒性研究。除了为NTP进行的动物研究外，我们还开始了一项在NIEHS临床研究单位招募的人类受试者中的研究，旨在将我们在动物中的发现转化为人类的潜在生物学效应，这些人经常使用NTP在啮齿动物模型中广泛分析的草药产品。