DEVELOPMENT OF A HUMAN SOMATIC GENE MUTAGENICITY ASSAY

人类体细胞基因突变性测定的开发

• 批准号: 6210363
• 负责人: EDWARD J YURKOW
• 金额: $ 10万
• 依托单位: MB RESEARCH LABORATORIES, INC.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6210363
• 关键词: DNA damage; cell differentiation; cell line; flow cytometry; gene expression; glycophorin; mutagen testing; mutagens; technology /technique development

DESCRIPTION (Adapted from the Investigator's Abstract): Industry and regulatory agencies are both in need of an improved test to characterize the mutagenic potential of drugs and chemicals. The present in vitro assays detect specific subtypes of DNA damage (i.e., insertions and deletions) of single-copy genes but do not detect mutation that may result during complex cellular processes such as homologous recombination and chromosome segregation. To address these and other limitations of the current mutagenicity screens, the investigator's group has conceptualized an in vitro test for somatic gene mutagenicity using a human erythroleukocyte cell line, a test is based on the widely used in vivo glycophorin A somatic cell mutation assay. This proposed assay would be able to detect mutagens based on their ability to induce the inactivation of an allele of a somatic gene. If developed to its full potential, this assay will complement the mutagenicity assays to screen drug formulations, chemicals and consumer products for human mutagens. This assay can be conducted in a high throughput format permitting the rapid screening of numerous compounds. PROPOSED COMMERCIAL APPLICATION: MB Research will offer this mutagenicity assay to the pharmaceutical, biotech, cosmetic, chemical and consumer products industries. Clients frequently make inquiries concerning alternatives to the Salmonella assay (Ames Test) and CHO/HGPRT mutagenicity assay. The proposed assay will have the ability to detect human mutagens that may be missed by the mutagenicity assays currently available. Since the proposed assay will satisfy an existing demand in the contract-testing industry for a test to detect specific types of human mutagens, the assay has tremendous commercial value.

描述（改编自研究者摘要）：行业和监管 两个机构都需要一种改进的测试来表征诱变性 毒品和化学品的潜力。本发明的体外测定法检测特异性 DNA损伤的亚型（即，插入和缺失）的单拷贝基因 但不能检测到在复杂的细胞过程中可能导致的突变 例如同源重组和染色体分离。解决这些 和当前致突变性筛选的其他局限性，研究者的 研究小组已经概念化了一种体外试验体细胞基因诱变性， 人红白细胞系，是一种在体内广泛应用的试验基础 血型糖蛋白A体细胞突变测定。这种拟议的分析将能够 根据诱变剂诱导等位基因失活的能力检测诱变剂 一个体细胞基因。如果充分发挥其潜力，该检测将 补充致突变性试验，以筛选药物制剂、化学品和 人类诱变剂的消费品。该测定可以在高浓度下进行。 通量格式允许快速筛选许多化合物。 拟定商业应用： MB Research将为制药，生物技术，化妆品， 化工和消费品行业。客户经常询问有关 沙门氏菌试验（艾姆斯试验）和CHO/HGPRT致突变性试验的替代品。 拟定试验将能够检测可能遗漏的人类诱变剂 通过目前可用的致突变性试验。 由于拟定的试验将满足 合同测试行业中对检测特定类型的 人类诱变剂，该检测具有巨大的商业价值。