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.

遗传毒性测试合同可评估NTP研究中潜在的不良遗传效应。所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）测定法。常规进行了三个主要测试：体外细菌诱变测定，体内啮齿动物外周血微核（MN）测定法和多个组织中的体内啮齿动物DNA损伤（彗星）测定。现在，MN分析通过对制备的血液样本进行流式细胞术分析，而不是通过评分幻灯片来收集数据。这种方法为检测诱导的染色体损伤提供了更大的能力，并提高了测试的客观性以及数据收集速度。 MN和彗星测定通常使用相同的动物进行，从而最大程度地收集了单个治疗动物的数据，减少动物使用情况并降低成本。在过去的会计年度中，已经开始或完成了大约11个微生物诱变分析和9个体内微核测定法。 40个体内彗星测定已在一个或多个组织中进行，包括血液，肝脏，肾脏，胃，结肠和大脑。在下一个会计年度中，预计将进一步强调基因突变和染色体损伤的体外测量，以便继续减少和完善我们对整个动物测试的使用。在过去的一个财政年度中，在未来在人类临床和生物监测研究中应用的另一个动物突变终点已在测试实验室中进行了研究：PIG-A突变测定法（磷脂酰肌醇聚糖锚固生物合成，A类基因）。在实验室啮齿动物的红细胞样品中很容易检测到该基因中的突变，并且已经开发了简化该测定法的更新方法，因此可以更多地将整合到现有的毒性测试中。在下一个财政年度，我们将尝试将该测定法与体内MN和彗星分析多样化，从而增加了我们从测试动物中获得的遗传毒性信息，以提供化学物质遗传毒性潜力的更全面的特征。目前，计划进行2项PIG-A研究，再加上将NTP毒性研究纳入现有的MN研究。除了针对NTP进行的动物工作外，我们还开始对NIEHS临床研究部门的人类受试者进行一项研究，旨在将我们的动物的发现转化为人类的潜在生物学作用，这些人经常使用草药产品，这些ntp在ntp中进行了广泛的分析。啮齿动物模型。